<!DOCTYPE html>
<html lang="en">

<head>
  <meta charset="utf-8" />
  <title>EPPI-Mapper</title>
  <style>
    *, *:before, *:after {
  box-sizing: border-box;
}
*:focus-visible {
  outline: 4px solid #000000;
}
html {
  box-sizing: border-box;
  font-family: 'Roboto', sans-serif;
  font-size: 14px;
  text-rendering: optimizeLegibility;
  -moz-osx-font-smoothing: grayscale;
  line-height: 1.5;
}
body {
  background-color: #ffffff;
  margin: 0;
  overflow: hidden;
}
a {
  color: #0275d8;
}
.clearfix:after {
  visibility: hidden;
  display: block;
  font-size: 0;
  content: " ";
  clear: both;
  height: 0;
}
* html .clearfix {
  zoom: 1;
}
*:first-child + html .clearfix {
  zoom: 1;
}
.loader {
  position: absolute;
  top: 0;
  right: 0;
  bottom: 0;
  left: 0;
  background: #000000;
  z-index: 1000;
  transition: all 2s ease;
}
.loader span.spinner {
  animation: spin 1.2s linear infinite;
  border: 5px solid #ffffff;
  border-bottom-color: #000000;
  border-top-color: #000000;
  border-radius: 100%;
  display: inline-block;
  width: 40px;
  height: 40px;
  position: absolute;
  top: 50%;
  left: 50%;
  transform: translate(-50%, -50%);
}
.header {
  padding: 0 18px;
}
.header-basic {
  background: #ffffff;
  padding: 0 18px;
  display: flex;
  font-size: 1.5rem; 
  font-weight: bold;
  height: 108px;
  padding: 8px 8px 0;
  text-align: center;
}
.header-basic .header-title {
  flex-grow: 1;
}
.header-basic .header-title span {
  position: relative;
  top: 30%;
}
.header-basic img {
  height: 100px;
}
.header-basic img:nth-child(1) {
  float: left;
}
.header-basic img:nth-child(2) {
  float: right;
}
.wrapper {
  margin: 8px;
}
.pivot-table {
  font-size: 11px;
  font-weight: normal;
  width: 100%;
}
.pivot-table .top-head, .pivot-table .side-head, .pivot-table .body,
.pivot-table .text-wrapp {
  display: inline-block;
  overflow: hidden;
}
.pivot-table .side-head, .pivot-table .body {
  float: left;
}
.pivot-table table {
  border: 0;
  border-collapse: collapse;
}
.pivot-table table thead th {
  border: 1px solid #ffffff;
  color: #ffffff;
  font-weight: normal;
  max-width: 103px;
  min-width: 103px;
  width: 103px;
  padding: 4px;
  overflow: hidden;
  text-overflow: ellipsis;
  vertical-align: top;
  text-align: left;
}
.pivot-table.text-view table thead th:not(.collapsed) {
  max-width: 153px;
  min-width: 153px;
  width: 153px;
}
.pivot-table.text-view-large table thead th:not(.collapsed) {
  max-width: 203px;
  min-width: 203px;
  width: 203px;
}
.pivot-table table tbody th, .pivot-table table tbody td {
  border: 1px solid #fff;
}
.pivot-table table tbody th {
  color: #ffffff;
  font-weight: normal;
  min-height: 103px;
  height: 103px;
  max-width: 103px;
  min-width: 0;
  width: 0;
  padding: 4px;
  overflow: hidden;
  text-overflow: ellipsis;
  vertical-align: top;
  text-align: left;
}
.pivot-table.text-view table tbody th:not(.collapsed) {
  min-height: 153px;
  height: 153px;
  max-width: 153px;
}
.pivot-table.text-view-large table tbody th:not(.collapsed) {
  min-height: 203px;
  height: 203px;
  max-width: 203px;
}
.pivot-table table tbody td {
  min-width: 103px;
  width: 103px;
  min-height: 103px;
  height: 103px;
}
.pivot-table.text-view table tbody td {
  min-width: 153px;
  width: 153px;
  min-height: 153px;
  height: 153px;
}
.pivot-table.text-view-large table tbody td {
  min-width: 203px;
  width: 203px;
  min-height: 203px;
  height: 203px;
}
.body table tbody td.cell div.data-wrapper {
  position: relative;
  background-color: #eeeeee;
  cursor: pointer;
  justify-items: center;
  align-items: center;
  width: 100%;
  height: 100%;
  overflow: hidden;
  -webkit-transition: all 0.5s;
  -moz-transition: all 0.5s;
  -moz-transition: all 0.5s;
  -ms-transition: all 0.5s;
  -o-transition: all 0.5s;
  transition: all 0.5s;
  flex-wrap: wrap;
  align-items: center;
  justify-content: space-around;
}
.body table tbody td.cell div.data-wrapper div.break {
  flex-basis: 100%;
  height: 0;
}
.body table tbody td.cell div.pie-wrapper {
  position: relative;
  background-color: #eeeeee;
  cursor: pointer;
  display: none;
  width: 100%;
  height: 100%;
  overflow: hidden;
}
.body table tbody td.cell div.mosaic-wrapper {
  position: relative;
  background-color: #eeeeee;
  cursor: pointer;
  display: none;
  width: 100px;
  height: 100px;
  max-width: 100px;
  max-height: 100px;
  overflow: hidden;
}
.body table tbody td.cell div.pie-wrapper div.pie,
.body table tbody td.cell div.pie-wrapper div.pie-hole{
  position: absolute;
  top: 50%;
  left: 50%;
  background-size: cover;
  border-radius: 100%;
  transform: translate(-50%, -50%);
}
.body table tbody td.cell div.pie-wrapper div.pie-hole{
  background-color: #dddddd;
}
.body table tbody td.cell.none div.data-wrapper,
.body table tbody td.cell.none div.pie-wrapper,
.body table tbody td.cell.none div.mosaic-wrapper {
  cursor: not-allowed !important;
}
.pivot-table.text-view .body table tbody td.cell div.data-wrapper div.data {
  display: flex;
  gap: 4px;
  align-items: center;
  padding: 2px;
}
.pivot-table.text-view .body table tbody td.cell div.data-wrapper div.data span.count {
  background: #ffffff;
  border: 1px solid #000000;
  border-radius: 2px;
  color: #000000;
  padding: 2px;
}
.controls {
  display: inline-block;
  position: absolute;
}
.ui-segment {
  background-color: #ffffff;
  color: #0275d8;
  border: 1px solid #0275d8;
  border-radius: 4px;
  display: inline-block;
}
.ui-segment span.option.active {
  background-color: #0275d8;
  color: #ffffff;
}
.ui-segment span.option {
  font-size: 13px;
  padding-left: 23px;
  padding-right: 23px;
  height: 25px;
  text-align: center;
  display: inline-block;
  line-height: 25px;
  margin: 0;
  float: left;
  cursor: pointer;
  border-right: 1px solid #0275d8;
  transition: all 0.5s ease;
}
.ui-segment span.option:last-child {
  border-right: none;
}
.segment-select{
  display: none;
}
.footer {
  position: absolute;
  bottom: 0;
  background-color: #ffffff;
  color: rgba(0, 0, 0, 0.87);
  height: 36px;
  min-height: 36px;
  padding: 16px;
  width: 100%;
  -webkit-box-align: center;
  -ms-flex-align: center;
  align-items: center;
  display: -webkit-box;
  display: -ms-flexbox;
  display: flex;
  -webkit-box-flex: 0 !important;
  -ms-flex: 0 1 auto !important;
  flex: 0 1 auto !important;
}
.footer .inner svg {
  display: inline-block;
  vertical-align: middle;
}
.footer .legend .dot {
  border-radius: 100%;
  display: inline-block;
  height: 10px;
  width: 10px;
  margin: 2px 3px 0 6px;
}
.footer .legend .label {
  font-size: 1.0em;
}
.legend-tooltip {
  border: 1px solid #cccccc;
  display: block;
  position: absolute;
  width: 300px;
  background: #ffffff;
  color: #000000;
  padding: 6px 8px;
  border-radius: 4px;
  -webkit-box-shadow: 0 2px 10px 2px rgba(0, 0, 0, 0.3);
  -moz-box-shadow: 0 2px 10px 2px rgba(0, 0, 0, 0.3);
  box-shadow: 0 2px 10px 2px rgba(0, 0, 0, 0.3);
  z-index: 2;
}
.spacer {
  -webkit-box-flex: 1 !important;
  -ms-flex-positive: 1 !important;
  flex-grow: 1 !important;
}
.hide {
  display: none;
}
.tooltip {
  display: none;
  position: absolute;
  border: 1px solid #cccccc;
  background-color: #ffffff;
  border-radius: 3px;
  padding: 3px 6px 2px;
  -webkit-box-shadow: 0 2px 10px 2px rgba(0, 0, 0, 0.3);
  -moz-box-shadow: 0 2px 10px 2px rgba(0, 0, 0, 0.3);
  box-shadow: 0 2px 10px 2px rgba(0, 0, 0, 0.3);
  z-index: 2;
}
.tooltip .count {
  color: #0275d8;
  margin: 2px 3px;
}
.tooltip .count span {
  background-color: #0275d8;
  -webkit-border-radius: 3px;
  -moz-border-radius: 3px;
  border-radius: 3px;
  color: #ffffff;
  padding: 2px 4px;
}
.refs {
  font-size:  12px;
  color:  lightgrey;
  margin:  0;
  padding: 0 0 0 20px;
}
.veil {
  background: rgba(0, 0, 0, 0.7);
  display: none;
  position: absolute;
  top: 0;
  right: 0;
  bottom: 0;
  left: 0;
  z-index: 99;
}
.veil.open {
  display: block;
}
.settings {
  position: absolute;
  top: 0;
  left: -600px;
  bottom: 0;
  background: #fff;
  color: #000000;
  padding: 0;
  width: 360px;
  z-index: 100;
}
.settings.open {
  left: 0;
}
.settings > div.title {
  color: #000000;
  font-size: 22px;
  padding: 20px;
  margin: 0 0 10px 0;
}
.settings > div.title > button.btnSettings {
  -webkit-border-radius: 36px;
  -moz-border-radius: 36px;
  border-radius: 36px;
  border: 1px solid #000000;
  background-color: inherit;
  color: #ffffff;
  background-color: #000000;
  display: inline-block;
  float: right;
  height: 36px;
  transition: all 0.25s ease;
  text-align: center;
  line-height: 36px;
  padding: 0 12px;
  letter-spacing: 1px;
}
.settings > div.title > button.btnSettings:hover {
  background-color: #ffffff;
  color: #000000;
  cursor: pointer;
}
.settings > div.title > button.btnSettings.busy{
  border: 3px solid #000000 !important;
  border-top-color: #ffffff !important;
  border-bottom-color: #ffffff !important;
  text-indent: -99999px;
  width: 36px;
  border-radius: 36px;
  animation: spin 1.2s linear infinite;
}
.settings > div.title > button.disabled {
  cursor: not-allowed;
  pointer-events: none;
  background: unset;
  color: #000000;
  opacity: 0.3;
  text-decoration: none;
}
.settings > div.title > button.right {
  border-bottom-left-radius: 0;
  border-top-left-radius: 0;
  margin-left: 2px;
}
.settings > div.title > button.left {
  border-bottom-right-radius: 0;
  border-top-right-radius: 0;
}
.settings div.filter-type-wrapper {
  background-color: #efefef;
  position: absolute;
  top: 76px;
  overflow: auto;
  padding: 0 10px 0 0;
  width: 100%;
  border-top: 1px solid #000000;
}
.settings div.filter-wrapper {
  background-color: #efefef;
  position: absolute;
  top: 226px;
  bottom: 0;
  overflow: auto;
  padding: 0 10px 0 0;
  width: 100%;
}
.settings div.filter-type-wrapper h2,
.settings div.filter-wrapper h2 {
  margin-left: 20px;
  margin-bottom: 10px;
}
.settings div.filter-type-wrapper ul,
.settings div.filter-wrapper ul {
  list-style: none;
  margin: 0 0 0 16px;
  padding: 0;
}
.settings div.filter-type-wrapper ul li,
.settings div.filter-wrapper ul li {
  margin: 0;
  padding: 3px 5px;
}
.settings div.filter-type-wrapper ul li:hover,
.settings div.filter-wrapper ul li:hover {
  cursor: pointer;
}
.settings div.filter-type-wrapper ul li span,
.settings div.filter-type-wrapper ul li svg,
.settings div.filter-wrapper ul li span,
.settings div.filter-wrapper ul li svg {
  display: inline-block;
  vertical-align: middle;
}
.settings div.filter-type-wrapper ul li svg,
.settings div.filter-wrapper ul li svg {
  display: none;
}
.settings div.filter-type-wrapper ul li.checked svg#checked,
.settings div.filter-wrapper ul li.checked svg#checked {
  display: inline-block;
}
.settings div.filter-type-wrapper ul li.unchecked svg#unchecked,
.settings div.filter-wrapper ul li.unchecked svg#unchecked {
  display: inline-block;
}
.settings div.filter-type-wrapper ul li.indeterminate svg#indeterminate,
.settings div.filter-wrapper ul li.indeterminate svg#indeterminate {
  display: inline-block;
}
.reader,
.accessibility {
  position: absolute;
  top: 0;
  right: -1000px;
  bottom: 0;
  background: #fff;
  color: #000;
  padding: 0;
  width: 1000px;
  z-index: 100;
}
.reader.open,
.accessibility.open {
  right: 0;
}
.reader > div.title,
.accessibility > div.title {
  background-color: #ffffff;
  color: #000000;
  display: flex;
  justify-content: space-between;
  font-size: 22px;
  padding: 20px;
}
.reader > div.title > div,
.accessibility > div.title > div {
  display: flex;
}
.reader > div.title > div:nth-child(1),
.accessibility > div.title > div:nth-child(1) {
  flex-grow: 1;
}
.reader > div.title > div:nth-child(1) > button,
.accessibility > div.title > div:nth-child(1) > button {
  margin-right: 18px;
}
.reader > div.title > div > input {
  border: 1px solid #000000;
  background: #ffffff;
  padding: 8px 16px;
  color: #000000;
  float: right;
  font-size: 16px;
  transition: all 0.5s ease;
  margin-right: 6px;
}
.reader > div.title > div > input:focus {
  background: #ffffff;
  color: #000000;
  box-shadow: 0 0 10px #719ECE;
}
.reader > div.title > div > input::-webkit-input-placeholder,
.reader > div.title > div > input::-moz-placeholder,
.reader > div.title > div > input:-ms-input-placeholder,
.reader > div.title > div > input:-moz-placeholder { 
  color: #595959;
}
.reader > div.title > div > select {
  border: 1px solid #000000;
  background: #ffffff;
  padding: 7.5px 16px;
  color: #595959;
  font-size: 16px;
  transition: all 0.5s ease;
  cursor: pointer;
  margin-right: 6px;
}
#filter-options option {
  color: #000000;
}
#filter-options option[value=""][disabled] {
  display: none;
}
.reader > div.content,
.accessibility > div.content {
  background: #ffffff;
  display: flex;
  align-content: stretch;
  align-items: stretch;
  height: 92.4%;
}
.reader > div.content > div.reader-filter {
  background-color: #efefef;
  border-right: 1px solid #ffffff;
  overflow: auto;
  width: 200px;
  min-width: 200px;
  max-width: 200px;
}
.reader > div.content > div.filter-opts {
  background-color: #efefef;
  border-right: 1px solid #ffffff;
  overflow: auto;
  width: 200px;
  min-width: 200px;
  max-width: 200px;
  float: right;
}
.settings > div.filter-wrapper > div.controlTainer {
  align-content: center;
  padding: 10px;
}
.reader > div.content > div.reader-filter ul {
  list-style: none;
  margin: 0;
  padding: 0;
  width: 100%;
  overflow: hidden;
}
.reader > div.content > div.reader-filter > ul > ul {
  padding: 0 0 0 12px;
 }
.reader > div.content > div.reader-filter ul li:hover {
  cursor: pointer;
}
.reader > div.content > div.reader-filter ul li {
  padding: 3px 6px 2px;
  display: inline-flex;
  align-items: end;
  width: 100%;
}
.reader > div.content > div.reader-filter ul li span,
.reader > div.content > div.reader-filter ul li svg {
  display: inline-block;
  vertical-align: middle;
}
.reader > div.content > div.reader-filter ul li svg {
  display: none;
  width: 24px;
  min-width: 24px;
}
.reader > div.content > div.reader-filter ul li span {
  white-space: nowrap;
  overflow: hidden;
  text-overflow: ellipsis;
}
.reader > div.content > div.reader-filter ul li.checked svg#checked {
  display: inline-block;
}
.reader > div.content > div.reader-filter ul li.unchecked svg#unchecked{
  display: inline-block;
}
.reader > div.content > div.reader-filter ul li.indeterminate svg#indeterminate {
  display: inline-block;
}
.reader > div.content > div.nav {
  background-color: #efefef;
  border-right: 1px solid #ffffff;
  overflow: auto;
  width: 280px;
  min-width: 280px;
  max-width: 280px;
}
.reader > div.content > div.navTainer {
  background-color: #efefef;
  border-right: 1px solid #ffffff;
  overflow: auto;
  width: 280px;
  min-width: 280px;
  max-width: 280px;
}
.reader > div.content > div.navTainer .navGroupSelect {
  color: #000000;
  border-top: 1px solid #000000;
  padding: 6px 10px 4px;
}
.reader > div.content > div.navTainer .ref-sort-order {
  color: #000000;
  border-top: 1px solid #000000;
  border-bottom: 1px solid #000000;
  padding: 6px 10px 4px;
}
.reader > div.content > div.navTainer > div.nav > ul,
.reader > div.content > div.navTainer > div.nav > ul.segmented,
.reader > div.content > div.navTainer > div.nav > ul.segmented > li > ul {
  list-style: none;
  margin: 0;
  padding: 0;
}
.refMenuItem {
  padding: 0;
  margin: 0;
}
.refMenuItem > button {
  color: #000000;
  background-color: transparent;
  border: 1px solid transparent;
  border-bottom-color: #ffffff;
  display: block;
  font-size: 1rem;
  padding: 6px 16px 8px;
  text-align: left;
  max-width: 280px;
}
.refMenuItem > button:hover,
.refMenuItem > button:focus-visible {
  background-color: #ffffff;
  cursor: pointer;
}
.refMenuItem > button > div.title,
.refMenuItem > button > div.auth {
  white-space: nowrap;
  overflow: hidden;
  text-overflow: ellipsis;
}
.refMenuItem > button > div.title {
  font-weight: bold;
}
.refMenuItem > button > div.auth,
.refMenuItem > button > div.date {
  color: #666666;
}
.refMenuItem > button > div.auth {
  font-style: italic;
}
.refMenuItem.selected > button {
  background-color: #000000;
  color: #ffffff;   
}
.refMenuItem.selected > button > div.auth,
.refMenuItem.selected > button > div.date {
  color: #cfcfcf;   
}
.reader > div.content > div.read,
.accessibility > div.content > div.read {
  flex-grow: 1;
  overflow: auto;
  padding: 10px 18px;
  border-top: 1px solid #000000;
}
.reader > div.content > div.read > h2,
.accessibility > div.content > div.read > h2 {
  margin-top: 0;
}
.reader > div.content > div.read > hr,
.accessibility > div.content > div.read > hr {
  background-color: #efefef;
  border: 0;
  height: 1px;
}
.reader > div.content > div.read > p,
.accessibility > div.content > div.read > p,
.accessibility > div.content > div.read > ul {
  font-size: 1.3rem;
}
.reader > div.content > div.read > div.meta-data {
  margin-top: 16px;
}
.reader > div.content > div.read > div.meta-data > div.meta-data-item > label {
  color: #aaaaaa;
  display: block;
  float: left;
  width: 140px;
  margin: 0 0 3px 0;
  padding: 3px 6px;
}
.reader > div.content > div.read > div.meta-data > div.meta-data-item > span {
  border: 1px solid #eeeeee;
  display: block;
  float: left;
  margin: 0 0 3px -140px;
  padding: 2px 4px 2px 144px;
  width: 100%;
}
.ref-sort-order {
  padding: 4px 8px;
}
.menu {
  background-color: #000000;
  border-bottom: 1px solid #000000;
  display: block;
  list-style: none;
  margin: 0;
  padding: 0;
}
.menu:after {
  content: "";
  display: table;
  clear: both;
}
.menu .menu-item {
  background-color: #000000;
  border: 0;
  color: #ffffff;
  display: flex;
  align-items: center;
  padding: 8px 12px;
  transition: all 0.2s ease-out;
  cursor: pointer;
  float: left;
  border: 0;
}
.menu .menu-item:active {
  background-color: #ffffff;
  color: #000000;
}
.menu .menu-item:active svg {
  fill: #000000;
}
.menu .menu-item:hover, .menu .menu-item:focus {
  background-color: #ffffff;
  color: #000000;
}
.menu .menu-item:hover svg, .menu .menu-item:focus svg {
  fill: #000000;
}
.menu .menu-item span {
  font-size: 14px;
  margin-left: 4px;
  overflow: hidden;
  word-break: keep-all;
}
.menu .menu-item svg {
  fill: #ffffff;
  display: inline-block;
  margin: 0 0 0 4px;
}
.menu .menu-item span.active-text,
.menu .menu-item svg.active-svg {
  display: none;
}
.menu .menu-item.active span.inactive-text,
.menu .menu-item.active svg.inactive-svg {
  display: none;
}
.menu .menu-item.active span.active-text,
.menu .menu-item.active svg.active-svg {
  display: block;
}
.menu .menu-item[aria-checked="true"] {
  background-color: #ffffff;
  color: #000000;
}
.menu .menu-item[aria-checked="true"] svg {
  fill: #000000;
}
.refMenuItemLegend {
  -webkit-border-radius: 100%;
  -moz-border-radius: 100%;
  border: 1px solid #ffffff;
  border-radius: 100%;
  display: inline-block;
  width: 10px;
  height: 10px;
  margin: 6px 3px 0;
  float: right;
}
.clickable-row,
.clickable-col {
  cursor: pointer;
}
.top-head th div,
.side-head th div {
  position: relative;
  width: 100%;
  height: 100%;
}
.top-head th div svg,
.side-head th div svg {
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  background: rgba(255, 255, 255, 0.8);
}
.top-head th div svg,
.side-head th div svg {
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}
.top-head th:not(.collapsed) div svg#arrowLeft,
.side-head th:not(.collapsed) div svg#arrowUp {
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}
.top-head th.collapsed div svg#arrowRight,
.side-head th.collapsed div svg#arrowDown {
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  display: inline-block;
}
.top-head th.busy div svg#refresh,
.side-head th.busy div svg#refresh {
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  cursor: pointer;
  display: inline-block;
  animation: spin 1s linear infinite;
}
.btnColCollapse,
.btnRowCollapse {
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}
.top-head th.collapsed {
  min-width: 0;
  max-width: 0;
  width: 0;
  padding: 4px 0;
}
.pivot-table .top-head th.collapsed.level-1 {
  min-width: 103px;
  width: 103px;
  padding: 4px;
}
.pivot-table.text-view .top-head th.collapsed.level-1 {
  min-width: 153px;
  width: 153px;
}
.pivot-table.text-view-large .top-head th.collapsed.level-1 {
  min-width: 203px;
  width: 203px;
}
.side-head th.collapsed {
  min-height: 0;
  max-height: 0;
  height: 0;
  padding: 0 4px;
}
.pivot-table .side-head th.collapsed.level-1 {
  min-height: 103px;
  height: 103px;
  padding: 4px;
}
.pivot-table.text-view .side-head th.collapsed.level-1 {
  min-height: 153px;
  height: 153px;
}
.pivot-table.text-view-large .side-head th.collapsed.level-1 {
  min-height: 203px;
  height: 203px;
}
.body td.collapsed-col {
  min-width: 18px;
  width: 18px;
}
.body td.collapsed-row {
  min-height: 18px;
  height: 18px !important;
}
.body td.collapsed-col,
.body td.collapsed-row {
  background: rgba(0, 0, 0, 0.2);
}
.body td.collapsed-col .mosaic-wrapper,
.body td.collapsed-row .mosaic-wrapper {
  width: auto !important;
  height: auto !important;
}
.body td.collapsed-col svg,
.body td.collapsed-row svg {
  display: none;
}
.body td.collapsed-col .pie-wrapper,
.body td.collapsed-col .mosaic-wrapper,
.body td.collapsed-col .data-wrapper,
.body td.collapsed-row .pie-wrapper,
.body td.collapsed-row .mosaic-wrapper,
.body td.collapsed-row .data-wrapper {
  opacity: 0 !important;
}
.top-head th.collapsed:not(.level-1) span,
.side-head th.collapsed:not(.level-1) span {
  display: none;
}
.top-head th.collapsed:not(.level-1),
.side-head th.collapsed:not(.level-1) {
  border-width: 0;
}
.top-head th.collapsed.first:not(.level-1) {
  border-left: 1px solid #ffffff !important;
}
.top-head th.collapsed.last:not(.level-1) {
  border-right: 1px solid #ffffff !important;
}
.side-head th.collapsed.first:not(.level-1) {
  border-top: 1px solid #ffffff !important;
}
.side-head th.collapsed.last:not(.level-1) {
  border-bottom: 1px solid #ffffff !important;
}
@keyframes spin {
  0% {
    transform: rotate(0deg);
  }
  100% {
    transform: rotate(360deg);
  }
}
.attribute-tooltip {
  position: absolute;
  border: 1px solid #cccccc;
  background-color: #ffffff;
  border-radius: 3px;
  display: none;
  padding: 3px 6px 2px;
  text-overflow: ellipsis;
  max-width: 350px !important;
  min-width: 200px !important;
  -webkit-box-shadow: 0 2px 10px 2px rgba(0, 0, 0, 0.3);
  -moz-box-shadow: 0 2px 10px 2px rgba(0, 0, 0, 0.3);
  box-shadow: 0 2px 10px 2px rgba(0, 0, 0, 0.3);
  z-index: 2;
}
.attribute-tooltip.show {
  display: block;
}
.attribute-tooltip .close-tooltip {
  cursor: pointer;
  float: right;
}
.attribute-tooltip .content {
  margin: 0 0 12px 0;
}
.attribute-tooltip h4 {
  margin: 0 0 8px 0;
}
.text-center {
  text-align: center;
}
.text-muted {
  color: #6c757d !important;
  font-size: 11px;
  margin: 10px 0 0 0;
}
#filterClearButton,
#codeFilterClearButton {
  float: right;
}
#codeFilterClearButton {
  width: 100%;
}
.btn {
  background-color: #000000;
  border: 1px solid #000000;
  color: #ffffff;
  display: block;
  font-weight: 400;
  padding: 8px 16px;
  font-size: 16px;
  line-height: normal;
  transition: color .15s ease-in-out,background-color .15s ease-in-out,border-color .15s ease-in-out,box-shadow .15s ease-in-out;
}
.btn:hover {
  color: #000000;
  background-color: inherit;
  border-color: #000000;
  cursor: pointer;
}
#status {
  display: none;
}
@keyframes spin {
  from {transform:rotate(0deg);}
  to {transform:rotate(360deg);}
}
.screenreader {
  position: absolute;
  left: -9999px;
}
.meta-data hr {
  border-top: 1px solid #000000;
}
#filterClearButton {
  padding: 6px 12px;
  border: 1px solid #000000;
  transition: all 0.25s ease;
  color: #ffffff;
  background-color: #000000;
}
#filterClearButton:hover {
  color: #000000;
  background-color: inherit;
}
#sgroup,
#RefSortOrder {
  border: 1px solid black;
  color: #595959;
}
#sgroup::placeholder,
#RefSortOrder::placeholder {
  color: #595959;
}
.style-picker {
  float: right !important;
}
  </style>
  <script type="text/javascript">
    var isIE = false || !!document.documentMode;

    if (isIE === true) {
      alert("Unfortunately this map cannot be used in Internet Explorer. You will need to use Microsoft Edge, Firefox or Google Chrome.");
    }
  </script>
</head>

<body>
  <p id="announce" class="screenreader" role="status" aria-live="polite"></p>
  <div class="attribute-tooltip">
    <span class="close-tooltip">X</span>
    <div class="content"></div>
  </div>
  <div class="loader">
    <span class="spinner"></span>
  </div>
  <div class="veil"></div>
  <div id="reader" class="reader" role="dialog" aria-labelledby="announce" style="display:none;"></div>
  <div id="accessibility" class="accessibility" role="dialog" aria-labelledby="announce" style="display:none;">
    <div class="title clearfix">
      <button class="btn close" aria-label="Close accessibility">X</button> <span>Accessibility</span>
    </div>
    <div class="content">
      <div class="read">
        <p>Web accessibility refers to the practice of designing and developing websites and web-based applications in a
          way that makes them usable and accessible to all individuals, including those with disabilities. This includes
          ensuring that web content can be easily understood, navigated, and interacted with by people with a wide range
          of abilities and disabilities, including those who use assistive technologies such as screen readers.</p>

        <p>This Eppi Mapper generated map conforms to the World Wide Web Consortium's Web Content Accessibility
          Guidelines (<a href="https://www.w3.org/WAI/standards-guidelines/wcag/" target="_blank">W3C WCAG</a>) Version
          2.1 Level AA to the maximum extent possible. These guidelines explain how to make web content more accessible
          for people with disabilities. The features in this map include:</p>

        <ul>
          <li>If the default settings have been used when generating this map, the overall colour design has been set to
            a more visually contrasting appearance.</li>
          <li>Links in the application have been converted to buttons to accommodate screen readers.</li>
          <li>Aria status updates now inform screen readers when modals open and selected records change.</li>
          <li>Tab focus is contained within opened modals.</li>
          <li>The style selection functionality has been moved to the top menu for easier access.</li>
          <li>A new style, Textual view, has been added to the map. This view presents the record counts within each
            node in a text readable format.</li>
          <li>URL links for individual records have been made descriptive.</li>
          <li>The map generation tool will inform the user if the selected background and font colour contrast meet
            accessibility requirements.</li>
        </ul>
        <br>
        <p><b>Limitations</b></p>
        <p>At the present time, while the keyboard focus does stay within each opened modal, the focus cannot be moved
          to individual checkboxes or radio buttons or, in the View Records modal, to all fields in the full record.
          This means that those items, along with the nodes in the map, can only be selected using a mouse or pointing
          device. In future updates we hope to address this limitation.</p>
      </div>
    </div>
  </div>
  <div class="menu" id="menu">
    <button class="menu-item menu-settings" role="button">
      <svg xmlns="http://www.w3.org/2000/svg" fill="#eeeeee" width="18" height="18" viewBox="0 0 24 24">
        <path d="M0 0h24v24H0z" fill="none" />
        <path
          d="M19.43 12.98c.04-.32.07-.64.07-.98s-.03-.66-.07-.98l2.11-1.65c.19-.15.24-.42.12-.64l-2-3.46c-.12-.22-.39-.3-.61-.22l-2.49 1c-.52-.4-1.08-.73-1.69-.98l-.38-2.65C14.46 2.18 14.25 2 14 2h-4c-.25 0-.46.18-.49.42l-.38 2.65c-.61.25-1.17.59-1.69.98l-2.49-1c-.23-.09-.49 0-.61.22l-2 3.46c-.13.22-.07.49.12.64l2.11 1.65c-.04.32-.07.65-.07.98s.03.66.07.98l-2.11 1.65c-.19.15-.24.42-.12.64l2 3.46c.12.22.39.3.61.22l2.49-1c.52.4 1.08.73 1.69.98l.38 2.65c.03.24.24.42.49.42h4c.25 0 .46-.18.49-.42l.38-2.65c.61-.25 1.17-.59 1.69-.98l2.49 1c.23.09.49 0 .61-.22l2-3.46c.12-.22.07-.49-.12-.64l-2.11-1.65zM12 15.5c-1.93 0-3.5-1.57-3.5-3.5s1.57-3.5 3.5-3.5 3.5 1.57 3.5 3.5-1.57 3.5-3.5 3.5z" />
      </svg>
      <span>Filters</span>
    </button>
    <button class="menu-item menu-expand" role="button">
      <svg class="inactive-svg" xmlns="http://www.w3.org/2000/svg" fill="#eeeeee" width="18" height="18"
        viewBox="0 0 24 24">
        <path
          d="M15 21h2v-2h-2v2zm4 0h2v-2h-2v2zM7 21h2v-2H7v2zm4 0h2v-2h-2v2zm8-4h2v-2h-2v2zm0-4h2v-2h-2v2zM3 3v18h2V5h16V3H3zm16 6h2V7h-2v2z" />
        <path d="M0 0h24v24H0z" fill="none" />
      </svg>
      <svg class="active-svg" xmlns="http://www.w3.org/2000/svg" fill="#eeeeee" width="18" height="18"
        viewBox="0 0 24 24">
        <path
          d="M13 7h-2v2h2V7zm0 4h-2v2h2v-2zm4 0h-2v2h2v-2zM3 3v18h18V3H3zm16 16H5V5h14v14zm-6-4h-2v2h2v-2zm-4-4H7v2h2v-2z" />
        <path d="M0 0h24v24H0z" fill="none" />
      </svg>
      <span class="inactive-text">Hide Headers</span>
      <span class="active-text" aria-hidden="true">Show Headers</span>
    </button>
    <button class="menu-item menu-fullscreen" role="button">
      <svg class="inactive-svg" xmlns="http://www.w3.org/2000/svg" fill="#eeeeee" width="18" height="18"
        viewBox="0 0 24 24">
        <path d="M0 0h24v24H0z" fill="none" />
        <path d="M7 14H5v5h5v-2H7v-3zm-2-4h2V7h3V5H5v5zm12 7h-3v2h5v-5h-2v3zM14 5v2h3v3h2V5h-5z" />
      </svg>
      <svg class="active-svg" xmlns="http://www.w3.org/2000/svg" fill="#eeeeee" width="18" height="18"
        viewBox="0 0 24 24">
        <path d="M0 0h24v24H0z" fill="none" />
        <path d="M5 16h3v3h2v-5H5v2zm3-8H5v2h5V5H8v3zm6 11h2v-3h3v-2h-5v5zm2-11V5h-2v5h5V8h-3z" />
      </svg>
      <span class="inactive-text">Fullscreen</span>
      <span class="active-text" aria-hidden="true">Exit Fullscreen</span>
    </button>
    <button class="menu-item menu-about" role="button">
      <svg xmlns="http://www.w3.org/2000/svg" fill="#eeeeee" width="18" height="18" viewBox="0 0 24 24">
        <path d="M0 0h24v24H0z" fill="none" />
        <path d="M12 2C6.48 2 2 6.48 2 12s4.48 10 10 10 10-4.48 10-10S17.52 2 12 2zm1 15h-2v-6h2v6zm0-8h-2V7h2v2z" />
      </svg>
      <span>About</span>
    </button>
    <button class="menu-item menu-studysubmit" role="button">
      <svg xlmns="http://www.w3.org/2000/svg" fill="#eeeeee" width="18" height="18" viewBox="0 0 24 24">
        <path d="M0 0h24v24H0z" fill="none" />
        <path
          d="M8.016 15l3.984-3.984 3.984 3.984-1.406 1.453-1.594-1.594v4.125h-1.969v-4.125l-1.594 1.547zM18 20.016v-11.016h-5.016v-5.016h-6.984v16.031h12zM14.016 2.016l6 6v12q0 0.797-0.609 1.383t-1.406 0.586h-12q-0.797 0-1.406-0.586t-0.609-1.383l0.047-16.031q0-0.797 0.586-1.383t1.383-0.586h8.016z">
        </path>
      </svg>
      <span>Submit a Study</span>
    </button>
    <button class="menu-item menu-reader" role="button">
      <svg xmlns="http://www.w3.org/2000/svg" fill="#eeeeee" width="18" height="18" viewBox="0 0 24 24">
        <path fill="none" d="M-74 29h48v48h-48V29zM0 0h24v24H0V0zm0 0h24v24H0V0z" />
        <path
          d="M13 12h7v1.5h-7zm0-2.5h7V11h-7zm0 5h7V16h-7zM21 4H3c-1.1 0-2 .9-2 2v13c0 1.1.9 2 2 2h18c1.1 0 2-.9 2-2V6c0-1.1-.9-2-2-2zm0 15h-9V6h9v13z" />
      </svg>
      <span>View Records<span class="record-count"></span></span>
    </button>
    <button class="menu-item menu-accessibility" role="button">
      <svg xmlns="http://www.w3.org/2000/svg" fill="#eeeeee" width="18" height="18" viewBox="0 0 18 18">
        <path
          d="M8 4.143A1.071 1.071 0 1 0 8 2a1.071 1.071 0 0 0 0 2.143Zm-4.668 1.47 3.24.316v2.5l-.323 4.585A.383.383 0 0 0 7 13.14l.826-4.017c.045-.18.301-.18.346 0L9 13.139a.383.383 0 0 0 .752-.125L9.43 8.43v-2.5l3.239-.316a.38.38 0 0 0-.047-.756H3.379a.38.38 0 0 0-.047.756Z" />
        <path d="M8 0a8 8 0 1 0 0 16A8 8 0 0 0 8 0ZM1 8a7 7 0 1 1 14 0A7 7 0 0 1 1 8Z" />
      </svg>
      <span>Accessibility</span>
    </button>
    <span class="style-picker" role="group">
      <button class="menu-item bubble-map selected" aria-checked="true" role="switch" aria-label="Bubble map"
        data-tippy-content="Bubble map view" data-style="bubble">
        <svg xmlns="http://www.w3.org/2000/svg" fill="#eeeeee" width="16" height="16" viewBox="0 0 16 16">
          <circle cx="8" cy="8" r="8" />
        </svg>
      </button>
      <button class="menu-item heat-map" aria-checked="false" role="switch" aria-label="Heat map view"
        data-tippy-content="Heat map view" data-style="heat">
        <svg xmlns="http://www.w3.org/2000/svg" fill="#eeeeee" width="16" height="16" viewBox="0 0 16 16">
          <path
            d="M8 15V1h6a1 1 0 0 1 1 1v12a1 1 0 0 1-1 1H8zm6 1a2 2 0 0 0 2-2V2a2 2 0 0 0-2-2H2a2 2 0 0 0-2 2v12a2 2 0 0 0 2 2h12z" />
        </svg>
      </button>
      <button class="menu-item mosaic-map" aria-checked="false" role="switch" aria-label="Mosaic map view"
        data-tippy-content="Mosaic map view" data-style="mosaic">
        <svg xmlns="http://www.w3.org/2000/svg" fill="#eeeeee" width="16" height="16" viewBox="0 0 16 16">
          <path d="M0 2a2 2 0 0 1 2-2h12a2 2 0 0 1 2 2v12a2 2 0 0 1-2 2H2a2 2 0 0 1-2-2V2z" />
        </svg>
      </button>
      <button class="menu-item donut-map" aria-checked="false" role="switch" aria-label="Donut map view"
        data-tippy-content="Donut map view" data-style="donut">
        <svg xmlns="http://www.w3.org/2000/svg" fill="#eeeeee" width="16" height="16" viewBox="0 0 16 16">
          <path d="M16 8A8 8 0 1 1 0 8a8 8 0 0 1 16 0zm-8 3a3 3 0 1 0 0-6 3 3 0 0 0 0 6z" />
        </svg>
      </button>
      <button class="menu-item text-map" aria-checked="false" role="switch" aria-label="Text map view"
        data-tippy-content="Text map view" data-style="text">
        <svg xmlns="http://www.w3.org/2000/svg" fill="#eeeeee" width="16" height="16" viewBox="0 0 16 16">
          <path
            d="M14.5 3a.5.5 0 0 1 .5.5v9a.5.5 0 0 1-.5.5h-13a.5.5 0 0 1-.5-.5v-9a.5.5 0 0 1 .5-.5h13zm-13-1A1.5 1.5 0 0 0 0 3.5v9A1.5 1.5 0 0 0 1.5 14h13a1.5 1.5 0 0 0 1.5-1.5v-9A1.5 1.5 0 0 0 14.5 2h-13z" />
          <path
            d="M3 5.5a.5.5 0 0 1 .5-.5h9a.5.5 0 0 1 0 1h-9a.5.5 0 0 1-.5-.5zM3 8a.5.5 0 0 1 .5-.5h9a.5.5 0 0 1 0 1h-9A.5.5 0 0 1 3 8zm0 2.5a.5.5 0 0 1 .5-.5h6a.5.5 0 0 1 0 1h-6a.5.5 0 0 1-.5-.5z" />
        </svg>
      </button>
    </span>
  </div>
  <div id="settings" class="settings" role="dialog" tabindex="-1" aria-labelledby="announce" style="display:none;">
  </div>
  <div class="header clearfix">
    
  </div>
  <div class="wrapper primary-view">
    <div class="pivot-table clearfix">
      <div class="top-head-wrapper">
        <div class="top-head">
          <table>
            <thead>
            </thead>
          </table>
        </div>
      </div>
      <div class="side-head">
        <table>
          <tbody>
          </tbody>
        </table>
      </div>
      <div class="body">
        <table>
          <tbody>
          </tbody>
        </table>
      </div>
    </div>
  </div>
  <div class="footer">
    <div class="legend"></div>
    <div class="spacer"></div>
    <div class="inner">
      Generated using v.2.3.0 of the EPPI-Mapper
      powered by <a href="https://eppi.ioe.ac.uk/cms/Default.aspx?tabid=2914" target="_blank">EPPI Reviewer</a>
      and created with
      <svg fill="#c62828" height="24" viewBox="0 0 24 24" width="24" xmlns="http://www.w3.org/2000/svg">
        <path d="M0 0h24v24H0z" fill="none" />
        <path
          d="M12 21.35l-1.45-1.32C5.4 15.36 2 12.28 2 8.5 2 5.42 4.42 3 7.5 3c1.74 0 3.41.81 4.5 2.09C13.09 3.81 14.76 3 16.5 3 19.58 3 22 5.42 22 8.5c0 3.78-3.4 6.86-8.55 11.54L12 21.35z" />
      </svg>
      by the
      <a href="http://www.digitalsolutionfoundry.co.za/" target="_blank">Digital Solution Foundry</a> team.
    </div>
  </div>
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  const referenceData = [{"Abstract":"With the development of modern medical informatics and databases, medical professionals are increasingly inclined to use evidence-based medicine to guide their learning and work. Evidence-based medicine requires a large amount of data and literature information, where most search processes are keyword retrieval. Therefore, anticipating these key information through the model can play an important role in optimizing the query. In the past, the PLM (Pre-trained Language Model) model was mainly used for information extraction, but due to the complexity of the sequence semantic structure and task diversity, it is difficult for traditional PLM to achieve the desired effect. With the advancement of LLM (Large Language Model) technology, these issues can now be well managed. In this paper, we discuss the information extraction evaluation task CHIP-PICOS, and finally decompose it into classification and information extraction sub-problems, applying PLM and LLM respectively, and analyzing the advantages and disadvantages and differences between PLM and LLM. The results show that our framework has achieved significant performance.","Authors":"Cao, Mengyuan, Wang, Hang, Liu, Xiaoming  et al.","Availability":"","City":"","Codes":[{"AttributeId":65,"ItemAttributeFullTextDetails":[]},{"AttributeId":1,"ItemAttributeFullTextDetails":[]},{"AttributeId":2,"ItemAttributeFullTextDetails":[]},{"AttributeId":3,"ItemAttributeFullTextDetails":[]},{"AttributeId":87,"ItemAttributeFullTextDetails":[]},{"AttributeId":96,"ItemAttributeFullTextDetails":[]},{"AttributeId":8,"ItemAttributeFullTextDetails":[]},{"AttributeId":9,"ItemAttributeFullTextDetails":[]},{"AttributeId":10,"ItemAttributeFullTextDetails":[]},{"AttributeId":23,"ItemAttributeFullTextDetails":[]},{"AttributeId":11,"ItemAttributeFullTextDetails":[]},{"AttributeId":14,"ItemAttributeFullTextDetails":[]},{"AttributeId":95,"ItemAttributeFullTextDetails":[]}],"Comments":"","Country":"","CreatedBy":"LS","DOI":"","DateCreated":"10/10/2024","DateEdited":"","EditedBy":"","Edition":"","Institution":"","Issue":"","ItemId":15192594,"ItemStatus":"","ItemStatusTooltip":"","Keywords":"","Month":"","OldItemId":"","Outcomes":[],"Pages":"","ParentAuthors":"","ParentTitle":"","Publisher":"","QuickCitation":"","ShortTitle":"","StandardNumber":"","Title":"LLM Collaboration PLM Improves Critical Information Extraction Tasks in Medical Articles","TypeName":"","URL":"https://link.springer.com/chapter/10.1007/978-981-97-1717-0_16","Volume":"","Year":"2024"},{"Abstract":"In recent years, the development of natural language process (NLP) technologies and deep learning hardware has led to significant improvement in large language models (LLMs). The ChatGPT, the state-of-the-art LLM built on GPT-3.5 and GPT-4, shows excellent capabilities in general language understanding and reasoning. Researchers also tested the GPTs on a variety of NLP-related tasks and benchmarks and got excellent results. With exciting performance on daily chat, researchers began to explore the capacity of ChatGPT on expertise that requires professional education for human and we are interested in the biomedical domain.To evaluate the performance of ChatGPT on biomedical-related tasks, this article presents a comprehensive benchmark study on the use of ChatGPT for biomedical corpus, including article abstracts, clinical trials description, biomedical questions, and so on. Typical NLP tasks like named entity recognization, relation extraction, sentence similarity, question and answering, and document classification are included. Overall, ChatGPT got a BLURB score of 58.50 while the state-of-the-art model had a score of 84.30. Through a series of experiments, we demonstrated the effectiveness and versatility of ChatGPT in biomedical text understanding, reasoning and generation, and the limitation of ChatGPT build on GPT-3.5.All the datasets are available from BLURB benchmark https://microsoft.github.io/BLURB/index.html. The prompts are described in the article.","Authors":"Chen, Qijie, Sun, Haotong, Liu, Haoyang  et al.","Availability":"","City":"","Codes":[{"AttributeId":1,"ItemAttributeFullTextDetails":[]},{"AttributeId":2,"ItemAttributeFullTextDetails":[]},{"AttributeId":3,"ItemAttributeFullTextDetails":[]},{"AttributeId":96,"ItemAttributeFullTextDetails":[]},{"AttributeId":53,"ItemAttributeFullTextDetails":[]},{"AttributeId":8,"ItemAttributeFullTextDetails":[]},{"AttributeId":9,"ItemAttributeFullTextDetails":[]},{"AttributeId":10,"ItemAttributeFullTextDetails":[]},{"AttributeId":23,"ItemAttributeFullTextDetails":[]},{"AttributeId":12,"ItemAttributeFullTextDetails":[]},{"AttributeId":13,"ItemAttributeFullTextDetails":[]},{"AttributeId":14,"ItemAttributeFullTextDetails":[]},{"AttributeId":94,"ItemAttributeFullTextDetails":[]}],"Comments":"","Country":"","CreatedBy":"LS","DOI":"","DateCreated":"10/10/2024","DateEdited":"","EditedBy":"","Edition":"","Institution":"","Issue":"","ItemId":15188615,"ItemStatus":"","ItemStatusTooltip":"","Keywords":"","Month":"","OldItemId":"","Outcomes":[],"Pages":"","ParentAuthors":"","ParentTitle":"","Publisher":"","QuickCitation":"","ShortTitle":"","StandardNumber":"","Title":"An extensive benchmark study on biomedical text generation and mining with ChatGPT","TypeName":"","URL":"https://openalex.org/works/W4386530347","Volume":"","Year":"2023"},{"Abstract":"Complete and transparent reporting of randomized controlled trial publications (RCTs) is essential for assessing their credibility. We aimed to develop text classification models for determining whether RCT publications report CONSORT checklist items. Using a corpus annotated with 37 fine-grained CONSORT items, we trained sentence classification models (PubMedBERT fine-tuning, BioGPT fine-tuning, and in-context learning with GPT-4) and compared their performance. We assessed the impact of data augmentation methods (Easy Data Augmentation (EDA), UMLS-EDA, text generation and rephrasing with GPT-4) on model performance. We also fine-tuned section-specific PubMedBERT models (e.g., Methods) to evaluate whether they could improve performance compared to the single full model. 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This potential automation is increasingly relevant as pharmaceutical developers face challenging requirements for timely and precise SLRs using the population, intervention, comparator and outcome (PICO) framework, such as those under the impending European Union (EU) Health Technology Assessment Regulation 2021/2282 (HTAR). This proof-of-concept study aimed to evaluate the feasibility, accuracy and efficiency of using GenAI for mass extraction of PICOs from PubMed abstracts.","Authors":"Reason, Tim, Langham, Julia, Gimblett, Andy","Availability":"","City":"","Codes":[{"AttributeId":3,"ItemAttributeFullTextDetails":[]},{"AttributeId":1,"ItemAttributeFullTextDetails":[]},{"AttributeId":2,"ItemAttributeFullTextDetails":[]},{"AttributeId":96,"ItemAttributeFullTextDetails":[]},{"AttributeId":8,"ItemAttributeFullTextDetails":[]},{"AttributeId":9,"ItemAttributeFullTextDetails":[]},{"AttributeId":10,"ItemAttributeFullTextDetails":[]},{"AttributeId":23,"ItemAttributeFullTextDetails":[]},{"AttributeId":15,"ItemAttributeFullTextDetails":[]},{"AttributeId":95,"ItemAttributeFullTextDetails":[]}],"Comments":"","Country":"","CreatedBy":"","DOI":"","DateCreated":"10/10/2024","DateEdited":"","EditedBy":"","Edition":"","Institution":"","Issue":"","ItemId":15188604,"ItemStatus":"","ItemStatusTooltip":"","Keywords":"","Month":"","OldItemId":"","Outcomes":[],"Pages":"","ParentAuthors":"","ParentTitle":"","Publisher":"","QuickCitation":"","ShortTitle":"","StandardNumber":"","Title":"Automated Mass Extraction of Over 680,000 PICOs from Clinical Study Abstracts Using Generative AI: A Proof-of-Concept Study","TypeName":"","URL":"https://openalex.org/works/W4402858850","Volume":"","Year":"2024"},{"Abstract":"Abstract In managing chronic diseases, the role of social determinants like lifestyle and diet is crucial. A comprehensive strategy combining biomedical and lifestyle changes is necessary for optimal health. However, the complexity of evidence from varied study designs on lifestyle interventions poses a challenge to decision-making. To tackle this challenge, our work focused on leveraging large language model to construct a dataset primed for evidence triangulation. This approach automates the process of gathering and preparing evidence for analysis, thereby simplifying the integration of reliable insights and reducing the dependency on labor-intensive manual curation. Our approach, validated by expert evaluations, demonstrates significant utility, especially illustrated through a case study on reduced salt intake and its effect on blood pressure. This highlights the potential of leveraging large language models to enhance evidence-based decision-making in health care.","Authors":"Shi, Xuanyu, Zhao, Wenjing, Wang, Jing  et al.","Availability":"","City":"","Codes":[{"AttributeId":41,"ItemAttributeFullTextDetails":[]},{"AttributeId":42,"ItemAttributeFullTextDetails":[]},{"AttributeId":18,"ItemAttributeFullTextDetails":[]},{"AttributeId":65,"ItemAttributeFullTextDetails":[]},{"AttributeId":1,"ItemAttributeFullTextDetails":[]},{"AttributeId":38,"ItemAttributeFullTextDetails":[]},{"AttributeId":3,"ItemAttributeFullTextDetails":[]},{"AttributeId":96,"ItemAttributeFullTextDetails":[]},{"AttributeId":25,"ItemAttributeFullTextDetails":[]},{"AttributeId":8,"ItemAttributeFullTextDetails":[]},{"AttributeId":20,"ItemAttributeFullTextDetails":[]},{"AttributeId":26,"ItemAttributeFullTextDetails":[]},{"AttributeId":9,"ItemAttributeFullTextDetails":[]},{"AttributeId":10,"ItemAttributeFullTextDetails":[]},{"AttributeId":23,"ItemAttributeFullTextDetails":[]},{"AttributeId":12,"ItemAttributeFullTextDetails":[]},{"AttributeId":13,"ItemAttributeFullTextDetails":[]},{"AttributeId":14,"ItemAttributeFullTextDetails":[]},{"AttributeId":50,"ItemAttributeFullTextDetails":[]},{"AttributeId":95,"ItemAttributeFullTextDetails":[]}],"Comments":"","Country":"","CreatedBy":"LS","DOI":"","DateCreated":"10/10/2024","DateEdited":"","EditedBy":"","Edition":"","Institution":"","Issue":"","ItemId":15188603,"ItemStatus":"","ItemStatusTooltip":"","Keywords":"","Month":"","OldItemId":"","Outcomes":[],"Pages":"","ParentAuthors":"","ParentTitle":"","Publisher":"","QuickCitation":"","ShortTitle":"","StandardNumber":"","Title":"EvidenceTriangulator: A Large Language Model Approach to Synthesizing Causal Evidence across Study Designs","TypeName":"","URL":"https://openalex.org/works/W4392939106","Volume":"","Year":"2024"},{"Abstract":"In the field of medical research, extracting PICOS information which includes population, intervention, Comparison, outcomes, and study design from medical papers, plays a significant role in improving search efficiency and guiding clinical practice. Based on the PICOS key information extraction task released from the China Health Information Processing Conference (CHIP 2023), we proposed a method based on Task-Specific Model Allocation, which selects different models according to the characteristics of the abstract and title data. Additionally, incorporating techniques such as multi-task learning and model fusion. Our method achieved first place on the leaderboard with an F1 score of 0.78 on List A and 0.81 on List B.","Authors":"Zhang, Qi, Qu, Jing, Zhao, Qingbo  et al.","Availability":"","City":"","Codes":[{"AttributeId":65,"ItemAttributeFullTextDetails":[]},{"AttributeId":1,"ItemAttributeFullTextDetails":[]},{"AttributeId":38,"ItemAttributeFullTextDetails":[]},{"AttributeId":3,"ItemAttributeFullTextDetails":[]},{"AttributeId":87,"ItemAttributeFullTextDetails":[]},{"AttributeId":96,"ItemAttributeFullTextDetails":[]},{"AttributeId":8,"ItemAttributeFullTextDetails":[]},{"AttributeId":9,"ItemAttributeFullTextDetails":[]},{"AttributeId":10,"ItemAttributeFullTextDetails":[]},{"AttributeId":23,"ItemAttributeFullTextDetails":[]},{"AttributeId":11,"ItemAttributeFullTextDetails":[]},{"AttributeId":14,"ItemAttributeFullTextDetails":[]},{"AttributeId":95,"ItemAttributeFullTextDetails":[]}],"Comments":"","Country":"","CreatedBy":"LS","DOI":"","DateCreated":"10/10/2024","DateEdited":"","EditedBy":"","Edition":"","Institution":"","Issue":"","ItemId":15188596,"ItemStatus":"","ItemStatusTooltip":"","Keywords":"","Month":"","OldItemId":"","Outcomes":[],"Pages":"","ParentAuthors":"","ParentTitle":"","Publisher":"","QuickCitation":"","ShortTitle":"","StandardNumber":"","Title":"Task-Specific Model Allocation Medical Papers PICOS Information Extraction","TypeName":"","URL":"https://openalex.org/works/W4392951372","Volume":"","Year":"2024"},{"Abstract":"In recent years, there has been a surge in the publication of clinical trial reports, making it challenging to conduct systematic reviews. 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Additionally, to showcase the highest effectiveness of LLM in oracle scenario where large number of annotated samples are available, we adopt the instruction tuning strategy by employing Low Rank Adaptation (LORA) to conduct the training of gigantic model in low resource environment for the PICO frame extraction task. More specifically, both of the proposed frameworks utilize AlpaCare as base LLM which employs both few-shot in-context learning and instruction tuning techniques to extract PICO-related terms from the clinical trial reports. We applied these approaches to the widely used coarse-grained datasets such as EBM-NLP, EBM-COMET and fine-grained datasets such as EBM-NLP(rev) and EBM-NLP(h). Our empirical results show that our proposed ICL-based framework produces comparable results on all the version of EBM-NLP datasets and the proposed instruction tuned version of our framework produces state-of-the-art results on all the different EBM-NLP datasets. Our project is available at https://github.com/shrimonmuke0202/AlpaPICO.git.","Authors":"Ghosh, M., Mukherjee, S., Ganguly, A.  et al.","Availability":"","City":"","Codes":[{"AttributeId":34,"ItemAttributeFullTextDetails":[]},{"AttributeId":3,"ItemAttributeFullTextDetails":[]},{"AttributeId":42,"ItemAttributeFullTextDetails":[]},{"AttributeId":33,"ItemAttributeFullTextDetails":[]},{"AttributeId":35,"ItemAttributeFullTextDetails":[]},{"AttributeId":1,"ItemAttributeFullTextDetails":[]},{"AttributeId":2,"ItemAttributeFullTextDetails":[]},{"AttributeId":96,"ItemAttributeFullTextDetails":[]},{"AttributeId":8,"ItemAttributeFullTextDetails":[]},{"AttributeId":9,"ItemAttributeFullTextDetails":[]},{"AttributeId":10,"ItemAttributeFullTextDetails":[]},{"AttributeId":23,"ItemAttributeFullTextDetails":[]},{"AttributeId":14,"ItemAttributeFullTextDetails":[]},{"AttributeId":15,"ItemAttributeFullTextDetails":[]},{"AttributeId":12,"ItemAttributeFullTextDetails":[]},{"AttributeId":13,"ItemAttributeFullTextDetails":[]},{"AttributeId":95,"ItemAttributeFullTextDetails":[]}],"Comments":"","Country":"","CreatedBy":"","DOI":"","DateCreated":"10/10/2024","DateEdited":"","EditedBy":"","Edition":"","Institution":"","Issue":"","ItemId":14800911,"ItemStatus":"","ItemStatusTooltip":"","Keywords":"","Month":"","OldItemId":"","Outcomes":[],"Pages":"","ParentAuthors":"","ParentTitle":"","Publisher":"","QuickCitation":"","ShortTitle":"","StandardNumber":"","Title":"AlpaPICO: Extraction of PICO frames from clinical trial documents using LLMs","TypeName":"","URL":"https://doi.org/10.1016/j.ymeth.2024.04.005","Volume":"","Year":"2024"},{"Abstract":"BACKGROUND: Initial insights into oncology clinical trial outcomes are often gleaned manually from conference abstracts. We aimed to develop an automated system to extract safety and efficacy information from study abstracts with high precision and fine granularity, transforming them into computable data for timely clinical decision-making. METHODS: We collected clinical trial abstracts from key conferences and PubMed (2012-2023). The SEETrials system was developed with four modules: preprocessing, prompt modeling, knowledge ingestion and postprocessing. We evaluated the system's performance qualitatively and quantitatively and assessed its generalizability across different cancer types- multiple myeloma (MM), breast, lung, lymphoma, and leukemia. Furthermore, the efficacy and safety of innovative therapies, including CAR-T, bispecific antibodies, and antibody-drug conjugates (ADC), in MM were analyzed across a large scale of clinical trial studies. RESULTS: SEETrials achieved high precision (0.958), recall (sensitivity) (0.944), and F1 score (0.951) across 70 data elements present in the MM trial studies Generalizability tests on four additional cancers yielded precision, recall, and F1 scores within the 0.966-0.986 range. Variation in the distribution of safety and efficacy-related entities was observed across diverse therapies, with certain adverse events more common in specific treatments. Comparative performance analysis using overall response rate (ORR) and complete response (CR) highlighted differences among therapies: CAR-T (ORR: 88%, 95% CI: 84-92%; CR: 95%, 95% CI: 53-66%), bispecific antibodies (ORR: 64%, 95% CI: 55-73%; CR: 27%, 95% CI: 16-37%), and ADC (ORR: 51%, 95% CI: 37-65%; CR: 26%, 95% CI: 1-51%). Notable study heterogeneity was identified (&gt;75% I (2) heterogeneity index scores) across several outcome entities analyzed within therapy subgroups. CONCLUSION: SEETrials demonstrated highly accurate data extraction and versatility across different therapeutics and various cancer domains. Its automated processing of large datasets facilitates nuanced data comparisons, promoting the swift and effective dissemination of clinical insights.","Authors":"Lee, K., Paek, H., Huang, L. C.  et al.","Availability":"","City":"","Codes":[{"AttributeId":1,"ItemAttributeFullTextDetails":[]},{"AttributeId":2,"ItemAttributeFullTextDetails":[]},{"AttributeId":75,"ItemAttributeFullTextDetails":[]},{"AttributeId":39,"ItemAttributeFullTextDetails":[]},{"AttributeId":17,"ItemAttributeFullTextDetails":[]},{"AttributeId":3,"ItemAttributeFullTextDetails":[]},{"AttributeId":60,"ItemAttributeFullTextDetails":[]},{"AttributeId":42,"ItemAttributeFullTextDetails":[]},{"AttributeId":65,"ItemAttributeFullTextDetails":[]},{"AttributeId":96,"ItemAttributeFullTextDetails":[]},{"AttributeId":8,"ItemAttributeFullTextDetails":[]},{"AttributeId":9,"ItemAttributeFullTextDetails":[]},{"AttributeId":10,"ItemAttributeFullTextDetails":[]},{"AttributeId":23,"ItemAttributeFullTextDetails":[]},{"AttributeId":12,"ItemAttributeFullTextDetails":[]},{"AttributeId":13,"ItemAttributeFullTextDetails":[]},{"AttributeId":14,"ItemAttributeFullTextDetails":[]},{"AttributeId":95,"ItemAttributeFullTextDetails":[]}],"Comments":"","Country":"","CreatedBy":"","DOI":"","DateCreated":"10/10/2024","DateEdited":"","EditedBy":"","Edition":"","Institution":"","Issue":"","ItemId":14800898,"ItemStatus":"","ItemStatusTooltip":"","Keywords":"","Month":"","OldItemId":"","Outcomes":[],"Pages":"","ParentAuthors":"","ParentTitle":"","Publisher":"","QuickCitation":"","ShortTitle":"","StandardNumber":"","Title":"SEETrials: Leveraging Large Language Models for Safety and Efficacy Extraction in Oncology Clinical Trials","TypeName":"","URL":"https://doi.org/10.1101/2024.01.18.24301502","Volume":"","Year":"2024"},{"Abstract":"BACKGROUND: The emergence of artificial intelligence, capable of human-level performance on some tasks, presents an opportunity to revolutionise development of systematic reviews and network meta-analyses (NMAs). In this pilot study, we aim to assess use of a large-language model (LLM, Generative Pre-trained Transformer 4 [GPT-4]) to automatically extract data from publications, write an R script to conduct an NMA and interpret the results. METHODS: We considered four case studies involving binary and time-to-event outcomes in two disease areas, for which an NMA had previously been conducted manually. For each case study, a Python script was developed that communicated with the LLM via application programming interface (API) calls. The LLM was prompted to extract relevant data from publications, to create an R script to be used to run the NMA and then to produce a small report describing the analysis. RESULTS: The LLM had a &gt; 99% success rate of accurately extracting data across 20 runs for each case study and could generate R scripts that could be run end-to-end without human input. It also produced good quality reports describing the disease area, analysis conducted, results obtained and a correct interpretation of the results. CONCLUSIONS: This study provides a promising indication of the feasibility of using current generation LLMs to automate data extraction, code generation and NMA result interpretation, which could result in significant time savings and reduce human error. This is provided that routine technical checks are performed, as recommend for human-conducted analyses. Whilst not currently 100% consistent, LLMs are likely to improve with time.","Authors":"Reason, T., Benbow, E., Langham, J.  et al.","Availability":"","City":"","Codes":[{"AttributeId":60,"ItemAttributeFullTextDetails":[]},{"AttributeId":42,"ItemAttributeFullTextDetails":[]},{"AttributeId":63,"ItemAttributeFullTextDetails":[]},{"AttributeId":49,"ItemAttributeFullTextDetails":[]},{"AttributeId":38,"ItemAttributeFullTextDetails":[]},{"AttributeId":96,"ItemAttributeFullTextDetails":[]},{"AttributeId":8,"ItemAttributeFullTextDetails":[]},{"AttributeId":10,"ItemAttributeFullTextDetails":[]},{"AttributeId":31,"ItemAttributeFullTextDetails":[]},{"AttributeId":9,"ItemAttributeFullTextDetails":[]},{"AttributeId":23,"ItemAttributeFullTextDetails":[]},{"AttributeId":15,"ItemAttributeFullTextDetails":[]},{"AttributeId":95,"ItemAttributeFullTextDetails":[]}],"Comments":"","Country":"","CreatedBy":"","DOI":"","DateCreated":"10/10/2024","DateEdited":"","EditedBy":"","Edition":"","Institution":"","Issue":"","ItemId":14800893,"ItemStatus":"","ItemStatusTooltip":"","Keywords":"","Month":"","OldItemId":"","Outcomes":[],"Pages":"","ParentAuthors":"","ParentTitle":"","Publisher":"","QuickCitation":"","ShortTitle":"","StandardNumber":"","Title":"Artificial Intelligence to Automate Network Meta-Analyses: Four Case Studies to Evaluate the Potential Application of Large Language Models","TypeName":"","URL":"https://doi.org/10.1007/s41669-024-00476-9","Volume":"","Year":"2024"},{"Abstract":"BACKGROUND: Systematic reviews of Randomized Controlled Trials (RCTs) are an important part of the evidence-based medicine paradigm. However, the creation of such systematic reviews by clinical experts is costly as well as time-consuming, and results can get quickly outdated after publication. Most RCTs are structured based on the Patient, Intervention, Comparison, Outcomes (PICO) framework and there exist many approaches which aim to extract PICO elements automatically. The automatic extraction of PICO information from RCTs has the potential to significantly speed up the creation process of systematic reviews and this way also benefit the field of evidence-based medicine. RESULTS: Previous work has addressed the extraction of PICO elements as the task of identifying relevant text spans or sentences, but without populating a structured representation of a trial. In contrast, in this work, we treat PICO elements as structured templates with slots to do justice to the complex nature of the information they represent. We present two different approaches to extract this structured information from the abstracts of RCTs. The first approach is an extractive approach based on our previous work that is extended to capture full document representations as well as by a clustering step to infer the number of instances of each template type. The second approach is a generative approach based on a seq2seq model that encodes the abstract describing the RCT and uses a decoder to infer a structured representation of a trial including its arms, treatments, endpoints and outcomes. Both approaches are evaluated with different base models on a manually annotated dataset consisting of RCT abstracts on an existing dataset comprising 211 annotated clinical trial abstracts for Type 2 Diabetes and Glaucoma. For both diseases, the extractive approach (with flan-t5-base) reached the best F1 score, i.e. 0.547 ( ±0.006 ) for type 2 diabetes and 0.636 ( ±0.006 ) for glaucoma. Generally, the F1 scores were higher for glaucoma than for type 2 diabetes and the standard deviation was higher for the generative approach. CONCLUSION: In our experiments, both approaches show promising performance extracting structured PICO information from RCTs, especially considering that most related work focuses on the far easier task of predicting less structured objects. In our experimental results, the extractive approach performs best in both cases, although the lead is greater for glaucoma than for type 2 diabetes. For future work, it remains to be investigated how the base model size affects the performance of both approaches in comparison. Although the extractive approach currently leaves more room for direct improvements, the generative approach might benefit from larger models.","Authors":"Witte, C., Schmidt, D. 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generative and extractive approaches to information extraction from abstracts describing randomized clinical trials","TypeName":"","URL":"https://doi.org/10.1186/s13326-024-00305-2","Volume":"","Year":"2024"},{"Abstract":"Meta-analysis of randomized clinical trials (rcts) plays a crucial role in evidence-based medicine but can be labor-intensive and error-prone. this study explores the use of large language models to enhance the efficiency of aggregating results from randomized clinical trials (rcts) at scale. we perform a detailed comparison of the performance of these models in zero-shot prompt-based information extraction from a diverse set of rcts to traditional manual annotation methods. we analyze the results for two different meta-analyses aimed at drug repurposing in cancer therapy pharmacovigilience in chronic myeloid leukemia. our findings reveal that the best model for the two demonstrated tasks, chatgpt can generally extract correct information and identify when the desired information is missing from an article. we additionally conduct a systematic error analysis, documenting the prevalence of diverse error types encountered during the process of prompt-based information extraction.","Authors":"Kartchner, David, Ramalingam, Selvi, Al-Hussaini, Irfan  et 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information extraction for clinical meta-analysis using large language models","TypeName":"","URL":"https://aclanthology.org/2023.bionlp-1.37","Volume":"","Year":"2023"},{"Abstract":"Results from randomized controlled trials (rcts) establish the comparative effectiveness of interventions, and are in turn critical inputs for evidence-based care. however, results from rcts are presented in (often unstructured) natural language articles describing the design, execution, and outcomes of trials; clinicians must manually extract findings pertaining to interventions and outcomes of interest from such articles. this onerous manual process has motivated work on (semi-)automating extraction of structured evidence from trial reports. in this work we propose and evaluate a text-to-text model built on instruction-tuned large language models (llms) to jointly extract interventions, outcomes, and comparators (ico elements) from clinical abstracts, and infer the associated results reported. manual (expert) and automated evaluations indicate that framing evidence extraction as a conditional generation task and fine-tuning llms for this purpose realizes considerable ($\\sim$20 point absolute f1 score) gains over the previous sota. we perform ablations and error analyses to assess aspects that contribute to model performance, and to highlight potential directions for further improvements. we apply our model to a collection of published rcts through mid-2022, and release a searchable database of structured findings: http://ico-relations.ebm-nlp.com","Authors":"Wadhwa, Somin, DeYoung, Jay, Nye, Benjamin  et 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extracting interventions, outcomes, and findings from rct reports with llms","TypeName":"","URL":"https://export.arxiv.org/abs/2305.03642","Volume":"","Year":"2023"},{"Abstract":"Plain language summarization with llms can be useful for improving textual accessibility of technical content. but how factual are these summaries in a high-stakes domain like medicine? this paper presents factpico, a factuality benchmark for plain language summarization of medical texts describing randomized controlled trials (rcts), which are the basis of evidence-based medicine and can directly inform patient treatment. factpico consists of 345 plain language summaries of rct abstracts generated from three llms (i.e., gpt-4, llama-2, and alpaca), with fine-grained evaluation and natural language rationales from experts. we assess the factuality of critical elements of rcts in those summaries: populations, interventions, comparators, outcomes (pico), as well as the reported findings concerning these. we also evaluate the correctness of the extra information (e.g., explanations) added by llms. using factpico, we benchmark a range of existing factuality metrics, including the newly devised ones based on llms. we find that plain language summarization of medical evidence is still challenging, especially when balancing between simplicity and factuality, and that existing metrics correlate poorly with expert judgments on the instance level.","Authors":"Joseph, Sebastian Antony, Chen, Lily, Trienes, Jan  et 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factuality evaluation for plain language summarization of medical evidence","TypeName":"","URL":"https://export.arxiv.org/abs/2402.11456","Volume":"","Year":"2024"},{"Abstract":"Meta-analyses statistically aggregate the findings of different randomized controlled trials (rcts) to assess treatment effectiveness. because this yields robust estimates of treatment effectiveness, results from meta-analyses are considered the strongest form of evidence. however, rigorous evidence syntheses are time-consuming and labor-intensive, requiring manual extraction of data from individual trials to be synthesized. ideally, language technologies would permit fully automatic meta-analysis, on demand. this requires accurately extracting numerical results from individual trials, which has been beyond the capabilities of natural language processing (nlp) models to date. in this work, we evaluate whether modern large language models (llms) can reliably perform this task. we annotate (and release) a modest but granular evaluation dataset of clinical trial reports with numerical findings attached to interventions, comparators, and outcomes. using this dataset, we evaluate the performance of seven llms applied zero-shot for the task of conditionally extracting numerical findings from trial reports. we find that massive llms that can accommodate lengthy inputs are tantalizingly close to realizing fully automatic meta-analysis, especially for dichotomous (binary) outcomes (e.g., mortality). however, llms -- including ones trained on biomedical texts -- perform poorly when the outcome measures are complex and tallying the results requires inference. this work charts a path toward fully automatic meta-analysis of rcts via llms, while also highlighting the limitations of existing models for this aim.","Authors":"Yun, Hye Sun, Pogrebitskiy, David, Marshall, Iain J.  et 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extracting numerical results from randomized controlled trials with large language models","TypeName":"","URL":"https://export.arxiv.org/abs/2405.01686","Volume":"","Year":"2024"},{"Abstract":"This paper describes a rapid feasibility study of using gpt-4, a large language model (llm), to (semi)automate data extraction in systematic reviews. despite the recent surge of interest in llms there is still a lack of understanding of how to design llm-based automation tools and how to robustly evaluate their performance. during the 2023 evidence synthesis hackathon we conducted two feasibility studies. firstly, to automatically extract study characteristics from human clinical, animal, and social science domain studies. we used two studies from each category for prompt-development; and ten for evaluation. secondly, we used the llm to predict participants, interventions, controls and outcomes (picos) labelled within 100 abstracts in the ebm-nlp dataset. overall, results indicated an accuracy of around 80%, with some variability between domains (82% for human clinical, 80% for animal, and 72% for studies of human social sciences). causal inference methods and study design were the data extraction items with the most errors. in the pico study, participants and intervention/control showed high accuracy (&gt;80%), outcomes were more challenging. evaluation was done manually; scoring methods such as bleu and rouge showed limited value. we observed variability in the llms predictions and changes in response quality. this paper presents a template for future evaluations of llms in the context of data extraction for systematic review automation. our results show that there might be value in using llms, for example as second or third reviewers. however, caution is advised when integrating models such as gpt-4 into tools. further research on stability and reliability in practical settings is warranted for each type of data that is processed by the llm.","Authors":"Schmidt, Lena, Hair, Kaitlyn, Graziozi, Sergio  et 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the use of a large language model for data extraction in systematic reviews: a rapid feasibility study","TypeName":"","URL":"https://export.arxiv.org/abs/2405.14445","Volume":"","Year":"2024"},{"Abstract":"Automatic medical discovery by ai is a dream of many. one step toward that goal is to create an ai model to understand clinical studies and synthesize clinical evidence from the literature. clinical evidence synthesis currently relies on systematic reviews of clinical trials and retrospective analyses from medical literature. however, the rapid expansion of publications presents challenges in efficiently identifying, summarizing, and updating evidence. we introduce trialmind, a generative ai-based pipeline for conducting medical systematic reviews, encompassing study search, screening, and data extraction phases. we utilize large language models (llms) to drive each pipeline component while incorporating human expert oversight to minimize errors. to facilitate evaluation, we also create a benchmark dataset trialreviewbench, a custom dataset with 870 annotated clinical studies from 25 meta-analysis papers across various medical treatments. our results demonstrate that trialmind significantly improves the literature review process, achieving high recall rates (0.897-1.000) in study searching from over 20 million pubmed studies and outperforming traditional language model embeddings-based methods in screening (recall@20 of 0.227-0.246 vs. 0.000-0.102). furthermore, our approach surpasses direct gpt-4 performance in result extraction, with accuracy ranging from 0.65 to 0.84. we also support clinical evidence synthesis in forest plots, as validated by eight human annotators who preferred trialmind over the gpt-4 baseline with a winning rate of 62.5%-100% across the involved reviews. our findings suggest that an llm-based clinical evidence synthesis approach, such as trialmind, can enable reliable and high-quality clinical evidence synthesis to improve clinical research efficiency.","Authors":"Wang, Zifeng, Cao, Lang, Danek, Benjamin  et 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    '<path d="M12 7c-2.76 0-5 2.24-5 5s2.24 5 5 5 5-2.24 5-5-2.24-5-5-5zm0-5C6.48 2 2 6.48 2 12s4.48 10 10 10 10-4.48 10-10S17.52 2 12 2zm0 18c-4.42 0-8-3.58-8-8s3.58-8 8-8 8 3.58 8 8-3.58 8-8 8z"/>' +
    '<path d="M0 0h24v24H0z" fill="none"/>' +
    '</svg>';
  const radioUncheckedSvg = '<svg id="unchecked" fill="#000000" height="24" viewBox="0 0 24 24" width="24" xmlns="http://www.w3.org/2000/svg">' +
    '<path d="M12 2C6.48 2 2 6.48 2 12s4.48 10 10 10 10-4.48 10-10S17.52 2 12 2zm0 18c-4.42 0-8-3.58-8-8s3.58-8 8-8 8 3.58 8 8-3.58 8-8 8z"/>' +
    '<path d="M0 0h24v24H0z" fill="none"/>' +
    '</svg>';
  const arrowUpSvg = '<svg class="btnRowCollapse arrowUp" id="arrowUp" fill="#000000" width="18" height="18" viewBox="0 0 24 24" xmlns="http://www.w3.org/2000/svg">' +
    '<path d="M20.24 18.804c0 0.116-0.058 0.247-0.145 0.334l-0.725 0.725c-0.087 0.087-0.203 0.145-0.334 0.145-0.116 0-0.247-0.058-0.334-0.145l-5.702-5.702-5.702 5.702c-0.087 0.087-0.218 0.145-0.334 0.145s-0.247-0.058-0.334-0.145l-0.725-0.725c-0.087-0.087-0.145-0.218-0.145-0.334s0.058-0.247 0.145-0.334l6.761-6.761c0.087-0.087 0.218-0.145 0.334-0.145s0.247 0.058 0.334 0.145l6.761 6.761c0.087 0.087 0.145 0.218 0.145 0.334zM20.24 13.232c0 0.116-0.058 0.247-0.145 0.334l-0.725 0.725c-0.087 0.087-0.203 0.145-0.334 0.145-0.116 0-0.247-0.058-0.334-0.145l-5.702-5.702-5.702 5.702c-0.087 0.087-0.218 0.145-0.334 0.145s-0.247-0.058-0.334-0.145l-0.725-0.725c-0.087-0.087-0.145-0.218-0.145-0.334s0.058-0.247 0.145-0.334l6.761-6.761c0.087-0.087 0.218-0.145 0.334-0.145s0.247 0.058 0.334 0.145l6.761 6.761c0.087 0.087 0.145 0.218 0.145 0.334z"/>' +
    '<path d="M0 0h24v24H0z" fill="none"/>' +
    '</svg>';
  const arrowDownSvg = '<svg class="btnRowCollapse arrowDown" id="arrowDown" fill="#000000" width="18" height="18" viewBox="0 0 24 24" xmlns="http://www.w3.org/2000/svg">' +
    '<path d="M20.24 12.768c0 0.116-0.058 0.247-0.145 0.334l-6.761 6.761c-0.087 0.087-0.218 0.145-0.334 0.145s-0.247-0.058-0.334-0.145l-6.761-6.761c-0.087-0.087-0.145-0.218-0.145-0.334s0.058-0.247 0.145-0.334l0.725-0.725c0.087-0.087 0.203-0.145 0.334-0.145 0.116 0 0.247 0.058 0.334 0.145l5.702 5.702 5.702-5.702c0.087-0.087 0.218-0.145 0.334-0.145s0.247 0.058 0.334 0.145l0.725 0.725c0.087 0.087 0.145 0.218 0.145 0.334zM20.24 7.196c0 0.116-0.058 0.247-0.145 0.334l-6.761 6.761c-0.087 0.087-0.218 0.145-0.334 0.145s-0.247-0.058-0.334-0.145l-6.761-6.761c-0.087-0.087-0.145-0.218-0.145-0.334s0.058-0.247 0.145-0.334l0.725-0.725c0.087-0.087 0.203-0.145 0.334-0.145 0.116 0 0.247 0.058 0.334 0.145l5.702 5.702 5.702-5.702c0.087-0.087 0.218-0.145 0.334-0.145s0.247 0.058 0.334 0.145l0.725 0.725c0.087 0.087 0.145 0.218 0.145 0.334z"/>' +
    '<path fill="none" d="M0 0h24v24H0V0z"/>' +
    '</svg>';
  const arrowLeftSvg = '<svg class="btnColCollapse arrowLeft" id="arrowLeft" fill="#000000" width="18" height="18" viewBox="0 0 24 24" xmlns="http://www.w3.org/2000/svg">' +
    '<path d="M14.436 19.036c0 0.116-0.058 0.247-0.145 0.334l-0.725 0.725c-0.087 0.087-0.218 0.145-0.334 0.145s-0.247-0.058-0.334-0.145l-6.761-6.761c-0.087-0.087-0.145-0.218-0.145-0.334s0.058-0.247 0.145-0.334l6.761-6.761c0.087-0.087 0.218-0.145 0.334-0.145s0.247 0.058 0.334 0.145l0.725 0.725c0.087 0.087 0.145 0.218 0.145 0.334s-0.058 0.247-0.145 0.334l-5.702 5.702 5.702 5.702c0.087 0.087 0.145 0.218 0.145 0.334zM20.008 19.036c0 0.116-0.058 0.247-0.145 0.334l-0.725 0.725c-0.087 0.087-0.218 0.145-0.334 0.145s-0.247-0.058-0.334-0.145l-6.761-6.761c-0.087-0.087-0.145-0.218-0.145-0.334s0.058-0.247 0.145-0.334l6.761-6.761c0.087-0.087 0.218-0.145 0.334-0.145s0.247 0.058 0.334 0.145l0.725 0.725c0.087 0.087 0.145 0.218 0.145 0.334s-0.058 0.247-0.145 0.334l-5.702 5.702 5.702 5.702c0.087 0.087 0.145 0.218 0.145 0.334z"/>' +
    '<path fill="none" d="M0 0h24v24H0V0z"/>' +
    '</svg>';
  const arrowRightSvg = '<svg class="btnColCollapse arrowRight" id="arrowRight" fill="#000000" width="18" height="18" viewBox="0 0 24 24" xmlns="http://www.w3.org/2000/svg">' +
    '<path d="M14.436 13c0 0.116-0.058 0.247-0.145 0.334l-6.761 6.761c-0.087 0.087-0.218 0.145-0.334 0.145s-0.247-0.058-0.334-0.145l-0.725-0.725c-0.087-0.087-0.145-0.218-0.145-0.334s0.058-0.247 0.145-0.334l5.702-5.702-5.702-5.702c-0.087-0.087-0.145-0.218-0.145-0.334s0.058-0.247 0.145-0.334l0.725-0.725c0.087-0.087 0.218-0.145 0.334-0.145s0.247 0.058 0.334 0.145l6.761 6.761c0.087 0.087 0.145 0.218 0.145 0.334zM20.008 13c0 0.116-0.058 0.247-0.145 0.334l-6.761 6.761c-0.087 0.087-0.218 0.145-0.334 0.145s-0.247-0.058-0.334-0.145l-0.725-0.725c-0.087-0.087-0.145-0.218-0.145-0.334s0.058-0.247 0.145-0.334l5.702-5.702-5.702-5.702c-0.087-0.087-0.145-0.218-0.145-0.334s0.058-0.247 0.145-0.334l0.725-0.725c0.087-0.087 0.218-0.145 0.334-0.145s0.247 0.058 0.334 0.145l6.761 6.761c0.087 0.087 0.145 0.218 0.145 0.334z"/>' +
    '<path fill="none" d="M0 0h24v24H0V0z"/>' +
    '</svg>';
  const refreshSvg = '<svg class="btnRefresh" id="refresh" fill="#000000" width="18" height="18" viewBox="0 0 24 24" width="24"><path d="M0 0h24v24H0z" fill="none"/><path d="M17.65 6.35C16.2 4.9 14.21 4 12 4c-4.42 0-7.99 3.58-7.99 8s3.57 8 7.99 8c3.73 0 6.84-2.55 7.73-6h-2.08c-.82 2.33-3.04 4-5.65 4-3.31 0-6-2.69-6-6s2.69-6 6-6c1.66 0 3.14.69 4.22 1.78L13 11h7V4l-2.35 2.35z"/></svg>';
  const topHeaderColors = ["#555555","#5a5a5a","#646464","#747474"];
  const topHeaderFontColor = "#FFFFFF";
  const sideHeaderColors = ["#555555","#5a5a5a","#646464","#747474"];
  const sideHeaderFontColor = "#FFFFFF";
  const dataColor = "#0275d8";
  const collapseColumnHeaders = undefined;
  const collapseRowHeaders = undefined;
  const allowRISDownload = true;
  const showRecordCount = false;
  const showColumnDescriptions = false;
  const showRowDescriptions = false;

  const $window = $(window);
  const $announce = $('#announce');
  const $pivotTable = $('.pivot-table');
  const $pivotBody = $('.body');
  const $textualBody = $('.textual-body');
  const $topHead = $('.top-head');
  const $textWrapp = $('.text-wrapp');
  const $topHeadTable = $('table', $topHead);
  const $topHeadWrapper = $('.top-head-wrapper');
  const $sideHead = $('.side-head');
  const $leftTable = $('.left-table');
  const $sideHeadTable = $('table', $sideHead);
  const $footer = $('.footer');
  const $menu = $('.menu');
  const $veil = $('.veil');
  const $reader = $('.reader');
  const $accessibility = $('.accessibility');
  const $attributeTooltip = $('.attribute-tooltip');
  const $attributeTooltipContent = $('.attribute-tooltip .content')
  const $recordCount = $('.record-count');

  let $header = $('.header');
  let chartType = 'bubble';
  let filterMode = 'default';

  //On page load force focus
  $(".menu").focus();
  $(document).ready(function () {
    var inputs = $('.menu').find('button').filter(':visible');

    var firstInput = inputs.first();
    var lastInput = inputs.last();

    /*set focus on first input*/
    firstInput.focus();

    /*redirect last tab to first input*/
    lastInput.on('keydown', function (e) {
      if ((e.which === 9 && !e.shiftKey)) {
        e.preventDefault();
        firstInput.focus();
      }
    });

    /*redirect first shift+tab to last input*/
    firstInput.on('keydown', function (e) {
      if ((e.which === 9 && e.shiftKey)) {
        e.preventDefault();
        lastInput.focus();
      }
    });
  });

  /**
   * @param {String} value
   */
  function safeParseInt(value) {
    const parsed = parseInt(value, 10);
    if (isNaN(parsed)) {
      return 0;
    }
    return parsed;
  }

  /**
   * Convert reference object from the eppi mapper to a RIS entry
   * @param referenceItem
   */
  function exportItemToRIS(reference, selectedKeywords) {
    const calend = [
      'Jan',
      'Feb',
      'Mar',
      'Apr',
      'May',
      'Jun',
      'Jul',
      'Aug',
      'Sep',
      'Oct',
      'Nov',
      'Dec',
    ];
    const newLine = '\r\n';
    let res = 'TY  - ';
    let tmp = '';
    switch (reference.TypeId) {
      case 14:
        res += 'JOUR' + newLine;
        break;
      case 1:
        res += 'RPRT' + newLine;
        break;
      case 2:
        res += 'BOOK' + newLine;
        break;
      case 3:
        res += 'CHAP' + newLine;
        break;
      case 4:
        res += 'THES' + newLine;
        break;
      case 5:
        res += 'CONF' + newLine;
        break;
      case 6:
        res += 'ELEC' + newLine;
        break;
      case 7:
        res += 'ELEC' + newLine;
        break;
      case 8:
        res += 'ADVS' + newLine;
        break;
      case 10:
        res += 'MGZN' + newLine;
        break;
      default:
        res += 'GEN' + newLine;
        break;
    }
    res += 'T1  - ' + reference.Title + newLine;
    if (reference.TypeId == 10 || reference.TypeId == 14)
      res += 'JF  - ' + reference.ParentTitle + newLine;
    else res += 'T2  - ' + reference.ParentTitle + newLine;
    for (let au of reference.Authors.split(';')) {
      tmp = au.trim();
      if (tmp != '') res += 'A1  - ' + tmp + newLine;
    }
    for (let au of reference.ParentAuthors.split(';')) {
      tmp = au.trim();
      if (tmp != '') res += 'A2  - ' + tmp + newLine;
    }
    res +=
      'KW  - eppi-reviewer4' +
      newLine +
      (reference.Keywords != null && reference.Keywords.length > 2
        ? reference.Keywords.trim() + newLine
        : '');
    let tmpDate = '';
    let Month = safeParseInt(reference.Month);

    if (!Month || Month < 1 || Month > 12) {
      Month =
        1 + reference.Month.length > 2
          ? calend.indexOf(reference.Month.substring(0, 3)) + 1
          : 0;
    }
    let yr = safeParseInt(reference.Year);
    if (reference.Year !== '' && yr) {
      if (yr > 0) {
        if (yr < 20) yr += 1900;
        else if (yr < 100) yr += 2000;
        if (yr.toString().length == 4) {
          res += 'PY  - ' + yr.toString() + newLine;
          if (Month != 0) {
            tmpDate +=
            reference.Year +
              '/' +
              (Month.toString().length == 1
                ? '0' + Month.toString()
                : Month.toString()) +
              '//';
          } else {
            tmpDate += reference.Year + '///' + reference.Month; //"y1  - "
          }
        }
      }
    }
    if (tmpDate.length > 0) {
      res += 'DA  - ' + tmpDate + newLine;
      res += 'Y1  - ' + tmpDate;

      //little trick: edition information is supposed to be the additional info at the end of the
      //Y1 filed. For Thesis pubtype (4) we use the edition field to hold the thesys type,
      //the following finishes up the Y1 field keeping all this into account

      if (reference.TypeId == 4 && reference.Edition.length > 0)
        res += newLine + 'KW  - ' + reference.Edition + newLine;
      else if (reference.Edition.length > 0) res += ' ' + reference.Edition + newLine;
      else res += newLine;
    } else if (reference.TypeId == 4 && reference.Edition.length > 0) {
      res += newLine + 'KW  - ' + reference.Edition + newLine;
    } //end of little trick

    res += 'AB  - ' + reference.Abstract + newLine;
    if (reference.DOI.length > 0) res += 'DO  - ' + reference.DOI + newLine;
    res += 'VL  - ' + reference.Volume + newLine;
    res += 'IS  - ' + reference.Issue + newLine;
    let split = '-';
    Yr = reference.Pages.indexOf(split);
    if (Yr > 0) {
      let pgs = reference.Pages.split(split);
      res += 'SP  - ' + pgs[0] + newLine;
      res += 'EP  - ' + pgs[1] + newLine;
    } else if (reference.Pages.length > 0) res += 'SP  - ' + reference.Pages + newLine;
    res +=
      'CY  - ' +
      reference.City +
      (reference.Country.length > 0 ? ' ' + reference.Country : '') +
      newLine;
    if (reference.URL.length > 0) res += 'UR  - ' + reference.URL + newLine;
    if (reference.Availability.length > 0) res += 'AV  - ' + reference.Availability + newLine;
    if (reference.Publisher.length > 0) res += 'PB  - ' + reference.Publisher + newLine;
    if (reference.StandardNumber.length > 0)
      res += 'SN  - ' + reference.StandardNumber + newLine;
    res += 'U1  - ' + reference.ItemId.toString() + newLine;
    res += 'U2  - ' + selectedKeywords + newLine;
    if (reference.OldItemId.length > 0) res += 'U3  - ' + reference.OldItemId + newLine;

    res += 'N1  - ' + reference.Comments + newLine;

    res += 'ER  - ' + newLine + newLine;

    res = res.replace('     ', ' ');
    res = res.replace('    ', ' ');
    res = res.replace('   ', ' ');
    res = res.replace('   ', ' ');
    return res;
  }

  /**
   *
   * @param {Array} references - array of eppi reference objects
   */
  function handleRisDownloadButtonClick(references){
    const $downloadButton = $('#risDownload');
    const selectedKeywords = $('li.checked', '.reader-filter').map(function() { return $(this).text().trim() }).get().join('; ');

    // remove existing onclick handlers
    $downloadButton.unbind();
    $downloadButton.on('click', (e) => {
      const fileBlob = createRISFile(references, selectedKeywords);
      downloadRISFile(fileBlob);
    });
  }

  /**
   * Create a RIS file blcb from the given references.
   * @param selectedReferences - list of references to create a RIS file from
   * @returns {Blob}
   */
  function createRISFile(selectedReferences, selectedKeywords){
    const len = selectedReferences.length;
    let risData = '';
    for(let i = 0; i < len; i++){
      risData += exportItemToRIS(selectedReferences[i], selectedKeywords);
    }
    return new Blob([risData], { type: 'text/plain' });

  }

  /**
   * Download the File blob of the references.
   * @param {Blob} file
  */
  function downloadRISFile(file){
    const blobUrl = URL.createObjectURL(file);
    // Save the need for file-save.js
    const link = document.createElement("a");
    link.href = blobUrl;
    link.download = `references.ris`;
    link.click();
  }

  /**
   * Gets the colour for the headings.
   * @param stepNumber
   * @returns {number}
   */
  function getColor(side, stepNumber) {
    // let base = 24;
    // let steps = 5;
    // let step = 8;
    //
    // // stops a step being greater than 5
    // stepNumber = stepNumber % steps;
    // return base + (step * stepNumber);
    stepNumber = stepNumber % 4;
    if (side)
      return sideHeaderColors[stepNumber];
    else
      return topHeaderColors[stepNumber];
  }

  /**
   * Builds the table used as the column headers of the pivot table.
   */
  function buildTableColHead() {
    let tableHeadHtml = '';
    let rowClass = '';
    let styles = [];

    for (let i = 0; i < csvData.totalColDepth; i++) {
      let cellClass = '';

      if (i > 0 && (i + 1) < csvData.totalColDepth) {
        rowClass = 'header-can-hide'
      } else if ((i + 1) === csvData.totalColDepth) {
        cellClass = 'clickable-col'
        rowClass = ''
      } else {
        rowClass = ''
      }

      const row = csvData.rows[i];
      tableHeadHtml += '<tr class="' + rowClass + '">';

      for (let j = 0; j < row.length; j++) {
        const col = row[j];

        const colSpan = i === 0 && j === 0 ? csvData.totalColBreadth : col.span;

        let style = '';
        let title = '';

        if (i === 0) {
          style = 'style="background-color:' + getColor(false, 0) + ';color:' + topHeaderFontColor + ';"';
        }

        if (i === 1) {
          style = 'style="background-color:' + getColor(false, j) + ';color:' + topHeaderFontColor + ';"';

          for (let k = 0; k < colSpan; k++)
          {
            styles.push(style);
          }
        }

        if (i > 1) {
          style = styles[j];
        }
        
        if (showColumnDescriptions && col.setDescription.length > 0) {
          title = col.setDescription;
        }

        tableHeadHtml += '<th class="level-' + i + ' ' + cellClass + '" colspan="' + colSpan + '" title="' + title + '" ' + style + ' data-id="' + col.id + '">';
        tableHeadHtml += '<div>';

        if (i === 1) {
          tableHeadHtml += arrowLeftSvg;
          tableHeadHtml += arrowRightSvg;
          tableHeadHtml += refreshSvg;
        }

        tableHeadHtml += '<span>';
        tableHeadHtml += col.title;
        tableHeadHtml += '</span></div>';
        tableHeadHtml += '</th>'
      }

      tableHeadHtml += '</tr>';
    }

    $('table thead', $topHead).append(tableHeadHtml);
    topColHeight = $('table', $topHead).height();
    $('table', $topHead).height(topColHeight);
  }

  /*
  Build text view table headers
  */
  function buildTextHeaderTable() {
    let textHead = '';
    let rowClass = '';
    let styles = [];

    for (let i = 0; i < csvData.totalColDepth; i++) {
      let cellClass = '';

      if (i > 0 && (i + 1) < csvData.totalColDepth) {
        rowClass = 'header-can-hide'
      } else if ((i + 1) === csvData.totalColDepth) {
        cellClass = 'clickable-col'
        rowClass = ''
      } else {
        rowClass = ''
      }

      const row = csvData.rows[i];
      textHead += '<tr class="' + rowClass + '">';

      for (let j = 0; j < row.length; j++) {
        const col = row[j];
        const colSpan = i === 0 && j === 0 ? csvData.totalColBreadth : col.span;

        let style = '';
        let title = '';

        if (i === 0) {
          style = 'style="background-color:' + getColor(false, 0) + ';color:' + topHeaderFontColor + ';"';
        }

        if (i === 1) {
          style = 'style="background-color:' + getColor(false, j) + ';color:' + topHeaderFontColor + ';"';

          for (let k = 0; k < colSpan; k++) {
            styles.push(style);
          }
        }

        if (i > 1) {
          style = styles[j];
        }

        if (showColumnDescriptions && col.setDescription.length > 0) {
          title = col.setDescription;
        }

        textHead += '<th class="table-width level-' + i + ' ' + cellClass + '" colspan="' + colSpan + '" title="' + title + '" ' + style + ' data-id="' + col.id + '">';
        textHead += '<div>';

        textHead += '<span>';
        textHead += col.title;
        textHead += '</span></div>';
        textHead += '</th>'
      }

      textHead += '</tr>';
    }

    $('table thead', $textWrapp).append(textHead);
    topColHeight = $('table', $textWrapp).height();
    $('table', $textWrapp).height(topColHeight);
  }

  /**
   * Builds the table used as the row headers of the pivot table.
   */
  function buildTableRowHead() {
    let tableHeadHtml = '';
    let rowClass = '';
    let lightnessLevel = 0;
    let backgroundStyle = '';

    for (let i = csvData.totalColDepth; i < csvData.rows.length; i++) {
      const row = csvData.rows[i];
      tableHeadHtml += '<tr>';

      for (let j = 0; j < row.length; j++) {
        const col = row[j];
        const rowSpan = i === csvData.totalColDepth && j === 0 ? csvData.totalRowBreadth : col.span;
        const level = csvData.totalColDepth - row.length + j;

        let title = '';

        if (level <= 0) {
          backgroundStyle = 'background-color:' + getColor(true, 0) + ';color:' + sideHeaderFontColor + ';';
        }

        if (level === 1) {
          backgroundStyle = 'background-color:' + getColor(true, lightnessLevel) + ';color:' + sideHeaderFontColor + ';';
          lightnessLevel += 1;
        }

        if (level > 0 && (level + 1) < csvData.totalColDepth) {
          rowClass = 'header-can-hide'
        } else if ((level + 1) === csvData.totalColDepth) {
          rowClass = 'clickable-row'
        }

        if (showRowDescriptions && col.setDescription.length > 0) {
          title = col.setDescription;
        }

        tableHeadHtml += '<th class="level-' + level + ' ' + rowClass + '" rowspan="' + rowSpan + '" title="' + title + '" style="' + backgroundStyle + '" data-id="' + col.id + '">';
        tableHeadHtml += '<div>';

        if (level === 1) {
          tableHeadHtml += arrowUpSvg;
          tableHeadHtml += arrowDownSvg;
          tableHeadHtml += refreshSvg;
        }

        tableHeadHtml += '<span>';
        tableHeadHtml += col.title;
        tableHeadHtml += '</span></div>';
        tableHeadHtml += '</th>'
      }

      tableHeadHtml += '</tr>';
    }

    $('table tbody', $sideHead).append(tableHeadHtml);
    sideColWidth = $('table', $sideHead).width();
    $('table', $sideHead).width(sideColWidth);
  }

  /**
   * Creates the table columns of a row for the pivot table.
   */
  function buildTableColumns(cols, $colHeaders, rowIds) {
    let colIndex = 0;
    let tableColHtml = '';

    $colHeaders.each(function(colHeaderIndex, colHeader) {
      const $colHeader = $(colHeader);
      const colSpan = parseInt($colHeader.attr('colspan'));

      if ($colHeader.hasClass('collapsed')) {
        const colIds = [];

        for (let i = 0; i < colSpan; i++) {
          colIds.push(cols[colIndex].id);
          colIndex++;
        }

        tableColHtml += '<td class="cell" ' +
          'data-colid="' + colIds.join(',') + '" ' +
          'data-rowid="' + rowIds.join(',') + '">' +
          '</td>';
      } else {
        for (let i = 0; i < colSpan; i++) {
          tableColHtml += '<td class="cell" ' +
            'data-colid="' + cols[colIndex].id + '" ' +
            'data-rowid="' + rowIds.join(',') + '">' +
            '</td>';
          colIndex++;
        }
      }
    });

    return tableColHtml;
  }

  /**
   * Creates the table rows of the pivot table.
   */
  function buildTableRows() {
    let tableRowHtml = '';
    let rowIndex = csvData.totalColDepth;

    const cols = csvData.rows[csvData.totalColDepth - 1];
    const $colHeaders = $('.top-head .level-1');
    const $rowHeaders = $('.side-head .level-1');

    $rowHeaders.each(function(rowHeaderIndex, rowHeader) {
      const rowIds = [];
      const $rowHeader = $(rowHeader);
      const rowSpan = parseInt($rowHeader.attr('rowspan'));

      if ($rowHeader.hasClass('collapsed')) {
        tableRowHtml += '<tr>';
        for (let i = 0; i < rowSpan; i++) {
          const row = csvData.rows[rowIndex];
          rowIds.push(row[row.length - 1].id);
          rowIndex++;
        }
        tableRowHtml += buildTableColumns(cols, $colHeaders, rowIds);
        tableRowHtml += '</tr>';
      } else {
        tableRowHtml += '<tr>';
        for (let i = 0; i < rowSpan; i++) {
          const row = csvData.rows[rowIndex];
          tableRowHtml += buildTableColumns(cols, $colHeaders, [row[row.length - 1].id]);
          rowIndex++;
          tableRowHtml += '</tr>';
        }
      }
    });

    $('table tbody', $pivotBody).html(tableRowHtml);
  }

  /**
   * Gets references that match the given row and column lists.
   * @param rowIdList
   * @param colIdList
   * @returns {Array}
   * @constructor
   */
  function getFilteredReferences(rowIdList, colIdList) {
    const references = [];
    const refMatches = referenceData
      .filter((reference) => {
        if (!reference.hasOwnProperty('Codes')) return false;

        //#region This Code Does All The Reader Filtering
        if (rowIdList.length > 0 && colIdList.length > 0) { // if we have selection in both column and row....
          for (const rowId of rowIdList) {  // for each row in the list of rows
            for (const colId of colIdList) {  // get a column in the list of columns
              if (reference.Codes // of the references that have codes,, does this particular reference have at least 2 codes that match rowid and colid
                .filter((code) => code.AttributeId === rowId || code.AttributeId === colId).length >= 2){
                  return true;
                }
            }
          }
        } else {
          for (const code of reference.Codes) {
            if (rowIdList.length === 0) {  // No row intersections to check for.
              if (colIdList.indexOf(code.AttributeId) >= 0) return true;
            } else if (colIdList.length === 0) {  // No column intersections to check for.
              if (rowIdList.indexOf(code.AttributeId) >= 0) return true;
            }
          }
        }
        //#endregion

        return false;
      });

    for (const reference of refMatches) {
      //#region does filtering in the settings menu (affects map display)
      if (filterMode === 'default'){
        //#region Check all the filters. (Parent AND > Child OR)
        const parentFilters = filters.filter((item) => item.checked);
        let refMatchesFilter = parentFilters.length === 0;

        for (const parentFilter of parentFilters) {
          refMatchesFilter = false;

          for (const childFilter of parentFilter.children.filter((item) => item.checked)) {
            const childFilterMatch = reference.Codes.filter((code) => code.AttributeId === childFilter.id).length > 0;

            if (childFilterMatch) {
              refMatchesFilter = true;
              break; // exit this loop --> immediately goes into execution of the parentFilter loop; leaves childfilter loops
                      // result is we end up not checking each selected child item for a match,, resulting in an "OR" condition; "AND" condition would include all selected child items
            }
          }

          // if we do not match in the child filters, then we know it's not AND and we
          // can break.
          if (!refMatchesFilter) break;
        }

        // if we do not match all active parent filters then we do not count this.
        if (!refMatchesFilter) continue;

        references.push(reference);
        //#endregion
      } else if (filterMode === 'and') {
        //#region Check all the filters. (Parent AND == Child AND)
        const parentFilters = filters.filter((item) => item.checked);
        let refMatchesFilter = parentFilters.length === 0;

        for (const parentFilter of parentFilters) { // when checking each parent filter item,
          refMatchesFilter = false; // reset match to false
          const childFilters = parentFilter.children.filter((item) => item.checked);  // filter out child filter items

          for (const childFilter of childFilters) { // each child filter item
            refMatchesFilter = false; // reset match to false
            const childFilterMatch = reference.Codes.filter((code) => code.AttributeId === childFilter.id).length > 0;  // check if child filter item's code matches any reference code

            if (childFilterMatch) { // if child filter item matches at least 1 reference code,
              refMatchesFilter = true;  // set match to true
              // continue this loop --> we do not immediately go into execution of the parentFilter loop; stay in childfilter loops
              // result is we check each selected child item for a match, returning only references which do match, resulting in an "AND" condition
            } else {
              // refMatchesFilter = false;
              break;
            }
          }

          if (!refMatchesFilter) break;
        }

        if (!refMatchesFilter) continue;

        references.push(reference);
        //#endregion
      } else if (filterMode === 'or') {
        //#region Check all the filters. (Parent OR == Child OR)
        const parentFilters = filters.filter((item) => item.checked);
        let refMatchesFilter = parentFilters.length === 0;

        for (const parentFilter of parentFilters) {
          const childFilters = parentFilter.children.filter((item) => item.checked);

          for (const childFilter of childFilters) {
            const childFilterMatch = reference.Codes.filter((code) => code.AttributeId === childFilter.id).length > 0;

            if (childFilterMatch) {
              refMatchesFilter = true;
              break;
            }
          }

          if (!refMatchesFilter) continue;
        }

        if (!refMatchesFilter){
        } else {
          references.push(reference);
        }
        //#endregion
      }
      //#endregion
    }

    return references;
  }

  /**
   * Builds the legend.
   */
  function buildLegend() {
    if (segmentAttributes === null) return;

    let legendHtml = '';

    segmentAttributes.forEach((segment) => {
      legendHtml += '<span class="legend-item" data-description="' + segment.attribute.AttributeSetDescription + '">' +
          '<span class="dot" style="background-color: ' + segment.color + '"></span>' +
          '<span class="label">' + segment.attribute.AttributeName + '</span></span>'
    })

    $('.legend').html(legendHtml);
  }

  /**
   * Creates a pie png image as a data url.
   */
  function createPiePng(counts) {
    let currentPoint = 0;
    let conicGrad = '';

    for (const count of counts) {
      currentPoint += count.width;
      if (conicGrad.length > 0) conicGrad += ', ';
      conicGrad += count.color + ' 0 ' + currentPoint + '%';
    }

    if (currentPoint < 100) {
      if (conicGrad.length > 0) conicGrad += ', ';
      conicGrad += '#eeeeee 0';
    }

    const gradient = new ConicGradient({
      stops: conicGrad,
      size: 97
    });

    const png = gradient.png;

    // Clean up memory issues once we have our PNG.
    $(gradient.canvas).empty().remove();
    delete gradient.canvas;

    return png;
  }

  /**
   * Create the mosiac svg
   *
   * @param {Number} dimension
   * @param {Array} references
   */
  function createMosaic(dimension, references) {
    let x = 0;
    let y = 0;

    let html = `<svg width="100" height="100" xmlns="http://www.w3.org/2000/svg">
   <defs>
   <pattern id="grid" width="${dimension}" height="${dimension}" patternUnits="userSpaceOnUse">
   <path d="M ${dimension} 0 L 0 0 0 ${dimension}" fill="none" stroke="white" stroke-width="0.5" />
   </pattern>
   </defs >
    <rect width="100%" height="100%" fill="url(#grid)" />`;

    for (const ref of references) {
      html += `<rect width="${dimension}" height="${dimension}" fill="${ref}" x="${x}" y="${y}" stroke="white" stroke-width="0.5" />`;
      x += dimension;

      if (x > 90) {
        x = 0;
        y += dimension
      }
    }

    html += '</svg >';


    return html;
  }

  /**
   * Creates the initial zero counts for the block.
   * @param rowIds
   * @param colIds
   */
  function createInitialCounts(rowIds, colIds) {
    let counts = [];

    if (segmentAttributes.length === 0) {
      counts.push({
        id: rowIds.join('_') + '-' + colIds.join('_'),
        attribute: null,
        color: dataColor,
        count: 0,
        width: 0,
        size: 0
      })
    } else {
      for (const segment of segmentAttributes) {
        counts.push({
          id: segment.attribute.AttributeId,
          attribute: segment.attribute,
          color: segment.color,
          isLight: segment.isLight,
          count: 0,
          width: 0,
          size: 0
        })
      }
    }

    return counts
  }

  /**
   * Calculate the dimensions of the blocks that will go in the svg grid
   *
   * @param {Number} minRequiredBlocks minimum required mosiac tiles (equal to max number of references)
   * @param {Number} containerDimension dimensions of the container
   */
  function getBlockSize(minRequiredBlocks, containerDimension) {
    let number = Math.round(Math.sqrt(minRequiredBlocks));
    while (containerDimension % number != 0 && number < containerDimension) {
      number = number + 1;
    }
    return containerDimension / number;
  }

  /**
   * Updates all the reference counts and creates the visuals.
   */
  function updateReferenceCounts() {
    let maxCount = 0;

    // Remove old html and detach events.
    $('.cell', $pivotBody).off();
    $('.pie-wrapper').off().detach().remove();
    $('.data-wrapper').off().detach().remove();

    $('.cell', $pivotBody).each((index, cell) => {
      const $cell = $(cell);
      let colIds = $cell.data('colid')
      let rowIds = $cell.data('rowid');

      if (isNaN(colIds)) {
        colIds = colIds.split(',').map(id => parseInt(id));
      } else {
        colIds = [colIds]
      }

      if (isNaN(rowIds)) {
        rowIds = rowIds.split(',').map(id => parseInt(id));
      } else {
        rowIds = [rowIds]
      }

      const references = getFilteredReferences(rowIds, colIds);
      const counts = createInitialCounts(rowIds, colIds);

      let totalCount = 0;

      for (const reference of references) {
        for (const count of counts) {
          if (count.attribute === null) {
            totalCount += 1;
            count.count += 1;
            continue;
          }

          const countMatched = reference.Codes
            .filter((code) => code.AttributeId === count.id).length > 0

          if (countMatched) {
            count.count += 1;
            totalCount += 1;
          }
        }
      }

      if (totalCount === 0) {
        $cell.addClass('none');
      } else {
        $cell.removeClass('none');
      }

      if (totalCount > maxCount) {
        maxCount = totalCount
      }

      for (const count of counts) {
        count.width = totalCount === 0 || count.count === 0 ? 0 : Math.round(count.count / totalCount * 100);

        // Check if the count is a sane amount to see, if not, make it the minimum.
        if (count.width < 8 && count.count !== 0) count.width = 8
      }

      // Sort counts descending.
      counts.sort(function(a, b) { return b.count - a.count});

      $cell.data('totalSize', 0);
      $cell.data('totalCount', totalCount);
      $cell.data('counts', counts);

      let wrapper = '';

      if (counts.length > 0) {
        switch (chartType) {
          case 'bubble':
          case 'heat':
          case 'text':
            wrapper = '<div class="data-wrapper">'

            let counter = 1;

            for (const count of counts) {
              if (count.count === 0) continue;

              let style = 'background-color:' + count.color + ';';

              if (!count.isLight) {
                style += 'color:#ffffff;';
              }

              wrapper += '<div id="' + count.id + '" ' +
                'class="data" ' +
                'style="' + style + '">';

              if (chartType === 'text') {
                if (count.attribute !== null) {
                  wrapper += `<span class="count">${count.count}</span><span class="name">${count.attribute.AttributeName}</span>`;
                } else if (count.count > 1) {
                  wrapper += `<span class="count">${count.count}</span><span class="name">Records</span>`;
                } else {
                  wrapper += `<span class="count">${count.count}</span><span class="name">Record</span>`;
                }
              }

              wrapper += '</div>';

              if (chartType !== 'text' && counter % 2 === 0) {
                wrapper += '<div class="break"></div>'
              }

              counter ++;
            }

            wrapper += '</div>'

            break;
          case 'mosaic':
            wrapper = '<div class="mosaic-wrapper"></div>'
            break;
          case 'donut':
            const png = createPiePng(counts);
            const piePngStyle = png.length > 0 ? ' style="background-image: url(' + png + ')"' : '';
            wrapper = `<div class="pie-wrapper"><div class="pie"${piePngStyle}></div><div class="pie-hole"></div></div>`
            break;
        }
      }

      $cell.html(wrapper);
    });

    // Update the size of the chart elements.
    $('.cell', $pivotBody).each((index, cell) => {
      const $cell = $(cell);
      const totalCount = $cell.data('totalCount');
      const counts = $cell.data('counts');

      for (const count of counts) {
        count.size = count.count === 0 ? 0 : Math.round(count.count / maxCount * 100);
        // Check if the count is a sane amount to see, if not, make it the minimum.
        if (count.size < 8 && count.count !== 0) count.size = 8
      }

      let totalSize = totalCount === 0 ? 0 : Math.round(totalCount / maxCount * 100);
      // Check if the count is a sane amount to see, if not, make it the minimum.
      if (totalSize < 8 && totalCount !== 0) totalSize = 8

      $cell.data('counts', counts);
      $cell.data('totalSize', totalSize);
      $cell.data('maxCount', maxCount);
    });

    // Setup events.
    setupTooltips();
    handleTableClick();
  }

  /**
   * Switches between the bubble and heat-map views.
   */
  function updateTableDataView() {
    $('.cell', $pivotBody).each((index, cell) => {
      const $cell = $(cell);
      const counts = $cell.data('counts');
      const totalSize = $cell.data('totalSize');
      const totalWidth = $cell.data('totalWidth');
      const maxCount = $cell.data('maxCount');
      const blockSize = 100;

      switch (chartType) {
        case 'bubble':
          $('.data-wrapper', $cell).css({
            'display': 'flex'
          });
          $('.data', $cell).css({
            'border-radius': '100%'
          });
          break;
        case 'heat':
          $('.data-wrapper', $cell).css({
            'display': 'flex',
            'opacity': (totalSize / 100)
          });
          break;
        case 'mosaic':
          $('.mosaic-wrapper', $cell).css({
            'display': 'block'
          });
          const dimension = getBlockSize(maxCount, 100);
          // Get colours from segments
          const referenceColours = counts.map(x => new Array(x.count).fill(x.color));
          const references = [].concat.apply([], referenceColours);
          let mosaic = createMosaic(dimension, references);
          $('.mosaic-wrapper', $cell).html(mosaic)
          break;
        case 'donut':
          const circleSize = (blockSize * totalSize / 100);
          let holeSize = totalSize - (circleSize / blockSize * 24);
          if (holeSize < 0) holeSize = 0;

          $('.pie-wrapper', $cell).css({
            'display': 'block'
          });

          $('.pie', $cell).css({
            'width': circleSize + '%',
            'height': circleSize + '%'
          });

          $('.pie-hole', $cell).css({
            'width': holeSize + '%',
            'height': holeSize + '%'
          });
          break;
        case 'text':
          break;
      }

      if (chartType !== 'text') {
        let maxBlockSize = blockSize;

        if (segmentAttributes.length > 1) {
          maxBlockSize = blockSize / (segmentAttributes.length / 2);
        }

        for (const [index, count] of counts.entries()) {
          let size = blockSize * count.size / 100;

          // Check if the count is a sane amount to see, if not, make it the minimum.
          if (size < 8 && count.count !== 0) size = 8;
          else if (size > maxBlockSize && count.count !== 0) size = maxBlockSize;

          $('#' + count.id, $cell).css({
            'height': chartType === 'bubble' ? size + 'px' : '100%',
            'width': chartType === 'bubble' ? size + 'px' : count.width + '%'
          });
        }

        setTimeout(function () {
          $('.data-wrapper', $cell).css({
            'opacity': chartType === 'heat' ? totalWidth / 100 : 1
          });
        }, 500);
      }
    });
  }

  /**
   * Cross browser functionality to request full screen access.
   * https://developer.mozilla.org/en-US/docs/Web/API/Fullscreen_API#Toggling_fullscreen_mode
   */
  function toggleFullScreen() {
    if (!document.fullscreenElement &&    // alternative standard method
      !document.mozFullScreenElement && !document.webkitFullscreenElement && !document.msFullscreenElement ) {  // current working methods
      if (document.documentElement.requestFullscreen) {
        document.documentElement.requestFullscreen();
      } else if (document.documentElement.msRequestFullscreen) {
        document.documentElement.msRequestFullscreen();
      } else if (document.documentElement.mozRequestFullScreen) {
        document.documentElement.mozRequestFullScreen();
      } else if (document.documentElement.webkitRequestFullscreen) {
        document.documentElement.webkitRequestFullscreen(Element.ALLOW_KEYBOARD_INPUT);
      }
    } else {
      if (document.exitFullscreen) {
        document.exitFullscreen();
      } else if (document.msExitFullscreen) {
        document.msExitFullscreen();
      } else if (document.mozCancelFullScreen) {
        document.mozCancelFullScreen();
      } else if (document.webkitExitFullscreen) {
        document.webkitExitFullscreen();
      }
    }
  }

  /**
   * Helper function to build the full table.
   */
  function buildTable() {
    buildTableColHead();
    buildTextHeaderTable();
    buildTableRowHead();
    buildTableRows();

    // Update data in the table.
    updateReferenceCounts();
    updateTableDataView();
  }

  /**
   * Sets the filter state of the the given filter ID by either adding it or
   * removing it from a list of unchecked filter IDs.
   * @param checkFilters
   * @param filterId
   * @param klass
   */
  function setFilterState(checkFilters, filterId, klass) {
    for (const filter of checkFilters) {
      if (filterId === filter.id) {
        filter.checked = klass === 'checked' || klass === 'indeterminate';
      }

      if (filter.children.length > 0) {
        setFilterState(filter.children, filterId, klass);
      }
    }
  }

  /**
   * Updates the filter's parent node's state.
   * @param $target
   */
  function updateFilterParentNodeCheckedState($target) {
    let hasChecked = false;
    let hasUnchecked = false;
    let hasIndeterminate = false;

    $target.next().children().each(function () {
      const klass = $(this).attr('class');

      if (klass === 'checked') {
        hasChecked = true;
      } else if (klass === 'unchecked') {
        hasUnchecked = true;
      } else {
        hasIndeterminate = true;
      }
    })

    let klass = '';

    if (hasChecked && !hasUnchecked && !hasIndeterminate) {
      klass = 'checked'
    } else if (!hasChecked && hasUnchecked && !hasIndeterminate) {
      klass = 'unchecked'
    } else if ((hasChecked && hasUnchecked && !hasIndeterminate) ||
      (hasChecked && !hasUnchecked && hasIndeterminate) ||
      (!hasChecked && hasUnchecked && hasIndeterminate) ||
      (hasChecked && hasUnchecked && hasIndeterminate)) {
      klass = 'indeterminate'
    }

    if (klass.length > 0) {
      const filterId = $target.data('id');
      setFilterState(filters, filterId, klass);

      $target
        .removeClass($target.attr('class'))
        .addClass(klass);
    }
  }

  /**
   * Updates the filter's node state and calls it's children r
   * recursively.
   * @param $target
   * @param newKlass
   */
  function updateFilterNodeCheckedState($target, newKlass = '') {
    const klass = $target.attr('class');
    $('#filterClearButton').attr('disabled',false);

    if (newKlass.length === 0) {
      if (klass === 'checked') {
        newKlass = 'unchecked';
      } else {
        newKlass = 'checked';
      }
    }

    const $next = $target.next();

    if ($next.is('ul')) {
      $next.children().each(function () {
        updateFilterNodeCheckedState($(this), newKlass);
      })
    }

    if ($target.is('li')) {
      const filterId = $target.data('id');
      setFilterState(filters, filterId, newKlass);

      $target
        .removeClass(klass)
        .addClass(newKlass);

      const $parent = $target.parent().prev();
      updateFilterParentNodeCheckedState($parent);
    }
  }

  /**
   * Update's the filter type and the checked state of the radios.
   * @param $filters
   * @param $target
   */
  function updateFilterMode($filters, $target) {
    const klass = $target.attr('class');
    if (klass === 'checked') return;

    filterMode = $target.data('id');

    $('.filter-type-wrapper li', $filters)
        .removeClass('checked')
        .addClass('unchecked');
    $target
        .removeClass('unchecked')
        .addClass('checked');
  }

  /**
   * Creates a filter node recursively.
   * @param filters
   * @returns {string}
   */
  function createFilterNode(filters) {
    let filterHtml = '<ul>';

    for (const filter of filters) {
      filterHtml += '<li class="unchecked" data-id="' + filter.id + '">' +
        checkboxCheckedSvg +
        checkboxUncheckedSvg +
        checkboxIndeterminateSvg +
        ' <span>' + filter.label + '</span></li>';

      if (filter.children.length > 0) filterHtml += createFilterNode(filter.children);
    }

    filterHtml += '</ul>';
    return filterHtml;
  }

  /**
   * Creates the elements for the settings panel and hooks up
   * the events.
   */
  function createSettingsPanel() {
    const $filters = $('.settings');

    // Open filter if it should be auto open.
    if (autoOpenFilter) {
      $filters.css({display: 'block'});
      $filters.addClass('open');
      $veil.addClass('open');
      settingsFocusTrap.activate();
    }

    let settingsHtml = '<div class="title clearfix">' +
      '<span id="settingsTitle">Filters</span>' +
      '<button class="btnSettings right" id="close" role="button" aria-label="Close filters">close</button>' +
      '<button class="btnSettings left disabled" id="update" role="button" aria-label="Update filters">update</button>' +
      '</div>';
    settingsHtml += createFiltersPanel();

    $filters.html(settingsHtml);

    $('.filter-type-wrapper li', $filters).on('click', (e) => {
      updateFilterMode($filters, $(e.currentTarget));
      $('.disabled').removeClass('disabled');
      $('#update', $filters).on('click', handleUpdate);
    });

    $('.filter-wrapper li', $filters).on('click', (e) => {
      updateFilterNodeCheckedState($(e.currentTarget));
      $('.disabled').removeClass('disabled');
      $('#update', $filters).on('click', handleUpdate);
    });

    $('.menu-settings').on('click', function () {
      $filters.css({display: 'block'});
      $filters.addClass('open');
      $veil.addClass('open');
      $filters.focus();
      settingsFocusTrap.activate();
    });    

    $('#filterClearButton').on('click', function () {
      const $filterButton = $('#filterClearButton');
      const $filteritems = $('.filter-wrapper ul > li');

      for (const item of $filteritems) {
        const $item = $(item);
        updateFilterNodeCheckedState($item, 'unchecked');
      }
      $filterButton.attr('disabled', true);
      $('.disabled').removeClass('disabled');
      $('#update', $filters).on('click', handleUpdate);
    })

    $('#close', $filters).on('click', function () {
      if (!$('#update', $filters).hasClass('disabled')) {
        if (!confirm('You have not updated the map with your changes. Are you sure you want to close?')) {
          return;
        }
      }

      $filters.removeClass('open');
      $veil.removeClass('open');
      $filters.css({display: 'none'});
      settingsFocusTrap.deactivate();
      $('.menu-settings').focus();
    });

    // Close modal on escape key
    $filters.on('keydown', function (event) {
      if (event.key === "Escape") {
        if (!$('#update', $filters).hasClass('disabled')) {
          if (!confirm('You have not updated the map with your changes. Are you sure you want to close?')) {
            return;
          }
        }
  
        $filters.removeClass('open');
        $veil.removeClass('open');
        $filters.css({display: 'none'});
        settingsFocusTrap.deactivate();
        $('.menu-settings').focus();
      }
    });

    function handleUpdate() {
      const $update = $(this);
      $update.addClass('busy');

      setTimeout(() => {
        updateReferenceCounts();
        updateTableDataView();
        UpdateRecordCount();

        $filters.removeClass('open');
        $veil.removeClass('open');
        $update.removeClass('busy')
          .addClass('disabled');
        $update.off('click');
        $filters.css({display: 'none'});
        settingsFocusTrap.deactivate();
        $('.menu-settings').focus();
      }, 300);
    }
  }

  /**
   * Creates the filter section elements for the settings panel.
   * @returns {string}
   */
  function createFiltersPanel() {
    let filterHtml = `<div class="filter-type-wrapper">
        <h2>Filter mode</h2>
        <ul>
          <li class="${filterMode === 'default' ? 'checked': 'unchecked'}" data-id="default">
            ${radioCheckedSvg}
            ${radioUncheckedSvg}
            <span>Default <small>(OR within sections, AND across sections)</small></span>
          </li> 
          <li class="${filterMode === 'and' ? 'checked': 'unchecked'}" data-id="and">
            ${radioCheckedSvg}
            ${radioUncheckedSvg}
            <span>And</span>
          </li> 
          <li class="${filterMode === 'or' ? 'checked': 'unchecked'}" data-id="or">
            ${radioCheckedSvg}
            ${radioUncheckedSvg}
            <span>Or</span>
          </li> 
        </ul>
      </div>
      <div class="filter-wrapper">
        <h2>Filters</h2>`;
      filterHtml +=
      '<button id="filterClearButton">Clear Filter</button>';
    filterHtml += createFilterNode(filters);
    filterHtml +=
    '</div>';

    return filterHtml;
  }

  function handleStyleClicked(e) {
    const styleButtons = document.querySelectorAll('button[data-style]');

    chartType = e.currentTarget.dataset.style;

    for (var i = 0; i < styleButtons.length; i++) {
      styleButtons[i].ariaChecked = false;
    }

    e.currentTarget.ariaChecked = true;

    if (chartType === 'text') {
      $pivotTable.addClass('text-view');

      if (segmentAttributes.length > 4) {
        $pivotTable.addClass('text-view-large');
      }
    } else {
      $pivotTable.removeClass('text-view');
      $pivotTable.removeClass('text-view-large');
    }

    adjustTable();
    updateReferenceCounts();
    updateTableDataView();

    $announce.html('Map changed to ' + chartType + 'view.');
  }

  function setupStyleSwitch() {
    var styleButtons = document.querySelectorAll('button[data-style]');
    var donutStyleButton = document.querySelectorAll('button[data-style="donut"]');

    for (var i = 0; i < styleButtons.length; i++) {
      styleButtons[i].onclick = handleStyleClicked;
    }

    if (segmentAttributes.length === 0 && donutStyleButton.length > 0) {
      donutStyleButton[0].style.display = 'none';
    }
  }

  /**
   * Creates the tooltip for the cell as it's hovered over.
   */
  function setupTooltips() {
    $('.cell').hover((e) => {
      if (chartType === 'text') return;

      // Hover.
      const $target = $(e.currentTarget);
      const totalCount = $target.data('totalCount');

      if (totalCount <= 0) {
        return
      }

      const counts = $target.data('counts');

      let tooltipHtml = '<div class="tooltip">';

      for (const count of counts) {
        if (count.count === 0) continue;

        let title = 'Record';

        if (count.count > 1) {
          title = 'Records';
        }

        if (count.attribute !== null) {
          title = count.attribute.AttributeName
        }

        tooltipHtml += '<div class="count">' +
          '<span style="background-color: ' + count.color + ';">' + count.count + '</span> ' +
          title +
          '</div>';
      }

      tooltipHtml += '</div>';

      $(tooltipHtml)
        .appendTo('body')
        .fadeIn('fast');
    }, (e) => {
      // Hover out.
      $('.tooltip').remove();
      delete $('.tooltip');
    }).mousemove((e) => {
      $('.tooltip')
        .css({
          top: e.pageY + 10,
          left: e.pageX + 10
        });
    });
  }

  /**
   * Creates the meta item in the reader for the reference key
   * passed in.
   * @param key
   * @param reference
   * @returns {string}
   */
  function createMetaItem(key, reference) {
    let metaItem = '';
    const renameKeys = {
      'Journal': 'ParentTitle'
    }
    let tempKey = renameKeys[key];
    if (reference[tempKey] == undefined) {
      tempKey = key
    }

    if (tempKey !== summaryAttribute && reference[tempKey] !== undefined && reference[tempKey].length > 0) {

      let label = '';
      label = key

      metaItem += '<div class="meta-data-item clearfix ' + tempKey + '">';
      metaItem += '<label>' + label.replace(/([^A-Z])([A-Z])/g, '$1 $2') + '</label>';
      metaItem += '<span>' + reference[tempKey] + '</span>';
      metaItem += '</div>'
    }

    return metaItem;
  }

  /**
   * Creates the elements to read a review.
   * @param refId
   */
  function selectReference(refId) {
    const references = referenceData.filter((reference) => {
      return reference.ItemId === refId;
    });

    if (references.length === 0) {
      $('.read').html('');
      return;
    }

    const reference = references[0];
    let refHtml = '<h2>' + reference.Title + '</h2>';
    refHtml += '<hr>';

    if (reference.Abstract !== undefined && reference.Abstract.length > 0) {
      refHtml += '<p>' + reference.Abstract.replace(/\r/g, '<br>') + '</p>';
      refHtml += '<hr>';
    } else if (summaryAttribute.length > 0 && reference[summaryAttribute] !== undefined && reference[summaryAttribute].length > 0) {
      refHtml += '<p>' + reference[summaryAttribute].replace(/\r/g, '<br>') + '</p>';
      refHtml += '<hr>';
    }

    if (reference.URL !== undefined && reference.URL.length > 0) {
      refHtml += '<ol class="refs">';
      refHtml += '<li><a class="small" href="' + reference.URL + '" target="_blank"> Read full article:' + reference.Title + '</a></li>';

      if (reference.DOI === undefined || reference.DOI.length === 0) {
        refHtml += '</ol>';
        refHtml += '<hr>';
      }
    }

    if (reference.DOI !== undefined && reference.DOI.length > 0) {
      if (reference.URL === undefined || reference.URL.length === 0) {
        refHtml += '<ol class="refs">';
      }

      refHtml += '<li><a class="small" href="' + reference.DOI + '" target="_blank"> Read full article:' + reference.Title + '</a></li>';
      refHtml += '</ol>';
      refHtml += '<hr>';
    }

    refHtml += '<div class="meta-data">';
    for (const key of metaProperties) {
      refHtml += createMetaItem(key, reference);
    }

    var matchedExturlAttributes = [];
    refHtml += "<div> <hr>";
    // checking for matches with external Attribute URLs to display in reader
    for (const attribute of externalURLedAttributes) {
      matchedExturlAttributes = reference.Codes.filter(code =>
        code.AttributeId === attribute.AttributeId);
      if (matchedExturlAttributes.length > 0 && attribute.ExtURL !== "" && attribute.ExtURL !== undefined) {
        refHtml +=
        '<span>' + attribute.AttributeName + '<br>' +
          '<a href="' + attribute.ExtURL + '" target="_blank">' + attribute.ExtURL + '</a>' +
        '</span><br>';
      }
    }
    refHtml +='</div>';

    refHtml += '</div>';

    $('.read', $reader).html(refHtml);
    $('#Article').attr("aria-labeledby", "ArticleTitle" + refId);
    $announce.html(reference.Title + 'has been selected.');
  }

  /**
   * Updates the reader to show the newly filtered/changed references.
   * @param references
   */
  function updateReferenceReader(references, justOpened = false) {
    $('.refMenuItem').off();

    const readerOrder = $('#RefSortOrder').val();

    if (readerOrder === 'title') {
      references.sort(function (a, b) {
        if (a.Title > b.Title) return 1;
        else if (a.Title < b.Title) return -1;
        else return 0;
      });
    } else if (readerOrder === 'author') {
      references.sort(function (a, b) {
        if (a.Authors > b.Authors) return 1;
        else if (a.Authors < b.Authors) return -1;
        else return 0;
      });
    } else if (readerOrder === 'date') {
      references.sort(function (a, b) {

        let aDateStr = '';
        let bDateStr = '';

        if (a.Month.length !== 0) {
          aDateStr += a.Month + ' 01, ';
        }
        aDateStr += a.Year;

        if (b.Month.length !== 0) {
          bDateStr += b.Month + ' 01, ';
        }
        bDateStr += b.Year;

        const aDate = Date.parse(aDateStr);
        const bDate = Date.parse(bDateStr);

        if (aDate > bDate) return 1;
        else if (aDate < bDate) return -1;
        else return 0;
      });
    }

    let title = '';
    let textToRead = '';

    if (justOpened) {
      textToRead = 'Reader modal opened. '
    }

    if (references.length === 0) {
      textToRead += 'No search results available.'
    } else
    if (references.length === 1) {
      title = references.length + ' Record'
      textToRead += references.length + ' search result available.'
    } else {
      title = references.length + ' Records'
      textToRead += references.length + ' search results are available.'
    }

    $groupingSelect = $('.grouping-opts');

    let refsHtml = '';

    if ($groupingSelect.val() === 'none') {   // no grouping
      //#region ADDS ALL THE STUDIES INTO AN UNSEGMENTED LIST
      refsHtml = '<ul>';

      for (const ref of references) {
        let colors = [];

        for (const code of ref.Codes) {
          for (const segment of segmentAttributes) {
            if (code.AttributeId === segment.attribute.AttributeId) {
              colors.push(segment.color);
            }
          }
        }

        refsHtml += '<li class="refMenuItem" data-refid="' + ref.ItemId + '" segmented="no">' +
          '<button aria-controls="Article">' +
          '<div class="title" id="ArticleTitle' + ref.ItemId + '">' + ref.Title + '</div>' +
          '<div class="auth">' + ref.Authors + '</div>';

        refsHtml += '<div class="date">';

        if (ref.Month.length !== 0) {
          refsHtml += ref.Month + ', ';
        }

        refsHtml += ref.Year;

        for (let color of colors) {
          refsHtml += '<span class="refMenuItemLegend" style="background-color: ' + color + '" />';
        }

        refsHtml += '</div>';
        refsHtml += '</button>';
        refsHtml += '</li>';
      }

      refsHtml += '</ul>';
      // #endregion
    } else if ($groupingSelect.val() === 'segment') {  // group by segments
      //#region ADD STUDIES INTO INDIVUDUAL UNORDERED LISTS
      refsHtml = '<ul class="segmented">';

      for (const segment of segmentAttributes){
        refsHtml +=
        '<li style="border-left:2px solid ' + segment.color + ';">' +
          '<div class="segment-title" style="border-bottom: 3px solid ' + segment.color + ';border-left: 5px solid ' + segment.color + '">'
            + segment.attribute.AttributeName +
          '</div>' +
          '<ul>';
            for (const ref of references) {
              let colors = [];

              for (const code of ref.Codes) {
                for (const segment of segmentAttributes){
                  if (code.AttributeId === segment.attribute.AttributeId) {
                    colors.push(segment.color);
                  }
                }
              }
              for (const code of ref.Codes) {
                if (code.AttributeId === segment.attribute.AttributeId) {
                  refsHtml +=
                  '<li class="refMenuItem" data-refid="' + ref.ItemId + '" segmented="yes">' +
                  '<button aria-controls="Article">' +
                  '<div class="title" id="ArticleTitle' + ref.ItemId + '">' + ref.Title + '</div>' +
                  '<div class="auth">' + ref.Authors + '</div>';

                  refsHtml += '<div class="date">';

                  if (ref.Month.length !== 0) {
                    refsHtml += ref.Month + ', ';
                  }

                  refsHtml += ref.Year;

                  for (let color of colors) {
                    refsHtml +=
                    '<span class="refMenuItemLegend" style="background-color: ' + color + '" />';
                  }

                  refsHtml += '</div>';
                  refsHtml += '</button>';
                  refsHtml += '</li>';
                }
              }
            }
          refsHtml +=
          '</ul>' +
        '</li>'
      }
      refsHtml +=
      '</ul>'
      //#endregion
    }

    // alert users on search results
    $announce.html(textToRead);
    $('.nav > ul', $reader).attr('id', 'results').attr('role', 'presentation');

    $('.title > div > span', $reader).html(title);
    $('.nav', $reader).html(refsHtml);

    $('.refMenuItem').on('click', (e) => {
      $('.refMenuItem').removeClass('selected');
      $('.rerefMenuItem > .title, .auth, .date').css('pointer-events','none');

      const $target = $(e.currentTarget);
      const refId = $target.data('refid');

      $target.addClass('selected');
      selectReference(refId);
    });

    if (references.length > 0) {
      $($('.refMenuItem')[0]).trigger('click');
    } else {
      selectReference(0);
    }

    handleRisDownloadButtonClick(references);
  }

  /**
   * Gets the reference code id's from the checked items in the reader
   * filter.
   * @returns {{rows: Array, cols: Array}}
   */
  function getReaderFilterSelection() {
    const colIdList = [];
    const rowIdList = [];

    $('.reader-filter .cols li').each((index, col) => {
      const $col = $(col);
      if ($col.attr('class') === 'checked') {
        colIdList.push($col.data('id'))
      }
    });

    $('.reader-filter .rows li').each((index, row) => {
      const $row = $(row);
      if ($row.attr('class') === 'checked') {
        rowIdList.push($row.data('id'))
      }
    });

    return {
      cols: colIdList,
      rows: rowIdList
    };
  }

  /**
   * Creates the reader selector HTML
   * @returns {string}
   */
  function buildReaderFilter(rowIdList, colIdList) {
    const readerTopFilter = csvData.rows[csvData.totalColDepth - 1]
    const readerSideFilter = []

    for (let i = csvData.totalColDepth; i < csvData.rows.length; i++) {
      const row = csvData.rows[i]
      readerSideFilter.push(row[row.length - 1])
    }

    let colParent = readerTopFilter.length === colIdList.length ? 'checked' : 'indeterminate';
    if (colIdList.length === 0) colParent = 'unchecked';

    let html = '<div class="reader-filter">' +
      '<button id="codeFilterClearButton" class="btn">Clear Filters</button>' +
      '<ul>' +
      '<li class="' + colParent + '" data-parent="true" title="' + csvData.rows[0][0].title + '">' +
      checkboxCheckedSvg +
      checkboxUncheckedSvg +
      checkboxIndeterminateSvg +
      ' <span>' + csvData.rows[0][0].title + '</span>' +
      '</li>' +
      '<ul class="cols">';

    for (const item of readerTopFilter)
    {
      const state = colIdList.indexOf(item.id) >= 0 ? 'checked' : 'unchecked';
      html += '<li class="' + state + '" data-id="' + item.id + '" data-parent="false" title="' + item.title + '">' +
        checkboxCheckedSvg +
        checkboxUncheckedSvg +
        checkboxIndeterminateSvg +
        ' <span>' + item.title + '</span>' +
        '</li>';
    }

    let rowParent = readerSideFilter.length === rowIdList.length ? 'checked' : 'indeterminate';
    if (rowIdList.length === 0) rowParent = 'unchecked';

    html += '</ul>';
    html += '<li class="' + rowParent + '" data-parent="true" title="' + csvData.rows[csvData.totalColDepth][0].title + '">' +
      checkboxCheckedSvg +
      checkboxUncheckedSvg +
      checkboxIndeterminateSvg +
      ' <span>' + csvData.rows[csvData.totalColDepth][0].title + '</span>' +
      '</li>';
    html += '<ul class="rows">';

    for (const item of readerSideFilter)
    {
      const state = rowIdList.indexOf(item.id) >= 0 ? 'checked' : 'unchecked';
      html += '<li class="' + state + '" data-id="' + item.id + '" data-parent="false" title="' + item.title + '">' +
        checkboxCheckedSvg +
        checkboxUncheckedSvg +
        checkboxIndeterminateSvg +
        ' <span>' + item.title + '</span>' +
        '</li>';
    }

    html += '</ul>';
    html += '</ul>';
    html += '</div>';
    return html
  }

  /**
   * Builds the reference reader.
   * @param selectedRowIds
   * @param selectedColIds
   */
  function buildReferenceReader(selectedRowIds, selectedColIds) {
    let risDownloadButton = '';

    if (allowRISDownload) {
      risDownloadButton = '<button id="risDownload" class="btn">Download Listed References</button>';
    }

    let readerHtml =
      '<div class="title clearfix">' +
        '<div>' +
        '<button class="btn close" aria-label="Close view records" role="button">X</button>' + 
        '<span></span>' +
        '</div><div>' +
        '<select id="filter-options" class="filter-opts">' +
          '<option class="opt-all" value="1"> All </option>' +
          '<option class="opt-title" value="2"> Title </option>' +
          '<option class="opt-abstract" value="3"> Abstract </option>' +
          '<option class="opt-author" value="4"> Author </option>' +
        '</select>' +
        '<input id="searchFilter" type="text" placeholder="Filter" class="reader-filter" aria-describedby="text-desc" aria-owns="results" aria-hidden="true" aria-activedescendant="">' +
        risDownloadButton +
        '</div>' +
      '</div>' +
      '<div class="content">' +
        buildReaderFilter(selectedRowIds, selectedColIds) +
        '<div class="navTainer">' +
          '<div class="navGroupSelect">' +
            '<label for="sgroup" style="width:70px;display:block;float:left;">Group by: </label>' +
            '<select id="sgroup" class="grouping-opts">' +
            '<option value="none">None</option>' +
            '<option value="segment">Segment</option>' +
            '</select>' +
          '</div>' +
          '<div class="ref-sort-order">' +
            '<label for="RefSortOrder" style="width:70px;display:block;float:left;">Sort by: </label>' +
            '<select id="RefSortOrder">' +
              '<option value="title">Title</option>' +
              '<option value="author">Author</option>' +
              '<option value="date">Date</option>' +
            '</select>' +
          '</div>' +
          '<div class="nav">' +
          '</div>' +
        '</div>' +
        '<div class="read" id="Article" role="region" aria-labeledby="" tabindex="-1"></div>' +
      '</div>';

    $reader.html(readerHtml);

    if (segmentAttributes.length <= 0) {
      $('.navGroupSelect').hide();
    }
  }

  /**
   * Performs the search on the reader.
   * @param event
   * @param references
   * @param $readerFilter
   * @param $filterSelect
   */
  function doReaderSearch(event, references, $readerFilter, $filterSelect) {
    if (event !== null && event.which === -1) return;

    const searchTerm = $readerFilter.val().toLowerCase().trim();
    const filterOption = $filterSelect.val();
    let searchReferences = [];

    if (searchTerm.length <= 0) {
      updateReferenceReader(references);
      return;
    }
    references.forEach((ref) => {
      if (filterOption == 1){   // search across All
        if (Object.keys(ref).indexOf('Abstract') > -1){
          let titleRefs = -1;
          let abstractRefs = -1;
          let authorRefs = -1;
          titleRefs = ref.Title.toLowerCase().indexOf(searchTerm);
          abstractRefs = ref.Abstract.toLowerCase().indexOf(searchTerm);
          authorRefs = ref.Authors.toLowerCase().indexOf(searchTerm);
          if (titleRefs !== -1 || abstractRefs !== -1 || authorRefs !== -1){
            searchReferences.push(ref);
          }
        }
      } else if (filterOption == 2){   // search by Title
        if (Object.keys(ref).indexOf('Title') > -1){
          if (ref.Title.toLowerCase().indexOf(searchTerm) !== -1){
            searchReferences.push(ref);
          }
        }
      } else if (filterOption == 3){   // search by Abstract
        if (Object.keys(ref).indexOf('Abstract') > -1){
          if (ref.Abstract.toLowerCase().indexOf(searchTerm) !== -1){
            searchReferences.push(ref);
          }
        }
      } else if (filterOption == 4){   // search by Author
        if (Object.keys(ref).indexOf('Authors') > -1){
          if (ref.Authors.toLowerCase().indexOf(searchTerm) !== -1){
            searchReferences.push(ref);
          }
        }
      }
    });

    // final line: always do the update
    updateReferenceReader(searchReferences);
  }

  function closeReader() {
    $reader.removeClass('open');
    $veil.removeClass('open');
    $reader.css({display: 'none'});
    $reader.html('');
    readerFocusTrap.deactivate();
  }

  /**
   * Shows the reader for the given row and column id lists.
   * @param rowIdList
   * @param colIdList
   */
  function toggleReader(rowIdList, colIdList) {
    const references = getFilteredReferences(rowIdList, colIdList);
    buildReferenceReader(rowIdList, colIdList);
    updateReferenceReader(references, true);
    const $readerFilter = $('.reader-filter');
    const $filterSelect = $('.filter-opts');

    // autofocus on the input on opening
    $reader.slideDown(function () {
      $("#searchFilter").focus();
    });

    $readerFilter.on('keydown', (e) => {
      doReaderSearch(e, references, $readerFilter, $filterSelect);
    });

    $filterSelect.on('change', (e) => {
      doReaderSearch(null, references, $readerFilter, $filterSelect);
    });

    $('.grouping-opts').on('change', (e) => {
      updateReferenceReader(references);
    });

    $('#RefSortOrder').on('change', (e) => {
      updateReferenceReader(references);
    });

    $('.reader-filter li').on('click', (e) => {
      const $target = $(e.currentTarget);
      const klass = $target.attr('class');
      const isParent = $target.data('parent');
      const newKlass = klass === 'checked' ? 'unchecked' : 'checked';
      $('#codeFilterClearButton').attr('disabled', false);

      $target
        .removeClass(klass)
        .addClass(newKlass);

      if (isParent) {
        $target.next().children().each((index, child) => {
          $(child)
            .removeClass('checked')
            .removeClass('unchecked')
            .addClass(newKlass);
        });
      } else {
        const parent = $target.parent().prev();
        $(parent)
          .removeClass('checked')
          .removeClass('unchecked')
          .addClass('indeterminate');
      }

      const newSelection = getReaderFilterSelection();
      const references = getFilteredReferences(newSelection.rows, newSelection.cols);

      updateReferenceReader(references);
    });

    $('#codeFilterClearButton').on('click', function() {
      const $filterItems = $('.reader-filter li');
      for (const item of $filterItems){
        const $item = $(item);
        if ($item.hasClass('unchecked')){
          // do nothing; already in target state
        } else if ($item.hasClass('checked')){
          $item.removeClass('checked');
          $item.addClass('unchecked');
        } else if ($item.hasClass('indeterminate')){
          $item.removeClass('indeterminate');
          $item.addClass('unchecked');
        }
      }

      $('#codeFilterClearButton').attr('disabled', true);
      const newSelection = getReaderFilterSelection();
      const references = getFilteredReferences(newSelection.rows, newSelection.cols);
      updateReferenceReader(references);
    });

    $reader.css({display: 'block'});
    $veil.addClass('open');
    $reader.addClass('open');
    readerFocusTrap.activate();

    // Close modal on escape key
    $reader.on('keydown', function (event) {
      if (event.key === "Escape") {
        closeReader();
      }
    });

    $('.close', $reader).on('click', () => {
      closeReader();
      $announce.html('View records closed.');
    });
  }

  /**
   * Creates the external url popup.
   * @param dataAxis
   * @param headerId
   * @param pageX
   * @param pageY
   */
  function createExtUrlPopup(dataAxis, headerId, pageX, pageY) {
    const filteredExtUrlAttr = externalURLedAttributes.filter(attr =>
      attr.AttributeId === headerId &&
      attr.AttributeName !== null &&
      attr.AttributeName !== undefined &&
      attr.AttributeName !== '' &&
      ((attr.AttributeDescription !== null &&
        attr.AttributeDescription !== undefined &&
        attr.AttributeDescription !== '') ||
        (attr.ExtURL !== undefined &&
        attr.ExtURL !== null &&
        attr.ExtURL !== '' &&
        attr.ExtType !== undefined &&
        attr.ExtType !== null &&
        attr.ExtType !== '')));
    const popupHasAttributeData = filteredExtUrlAttr.length > 0;

    if (!popupHasAttributeData) return false;

    let popUpHtml = '<div class="overlay-text" data-header-id="' + headerId + '" data-axis="' + dataAxis + '">';

    for (const attribute of filteredExtUrlAttr) {
      popUpHtml += '<h4>' + attribute.AttributeName + '</h4>';

      if (attribute.AttributeDescription !== null &&
        attribute.AttributeDescription !== undefined &&
        attribute.AttributeDescription.length > 0) {
        popUpHtml += '<p>' + attribute.AttributeDescription + '</p>';
      }

      if (attribute.ExtURL !== undefined &&
        attribute.ExtURL !== null &&
        attribute.ExtURL !== '' &&
        attribute.ExtType !== undefined &&
        attribute.ExtType !== null &&
        attribute.ExtType !== '') {
        popUpHtml += '<a class="overlay-link" href="' + attribute.ExtURL + '" target="_blank">' + attribute.ExtType + '</a>';
      }
    }

    popUpHtml += '<p class="text-center text-muted">(click to view records)</p></div>'

    $attributeTooltipContent.html(popUpHtml);
    $attributeTooltip.addClass('show');

    $('.close-tooltip').on('click', (e) => {
      $attributeTooltip.removeClass('show');
    });

    $attributeTooltipContent.on('click', (e) => {
      $attributeTooltip.removeClass('show');

      const $target = $('.overlay-text');
      const headerId = parseInt($target.data('header-id'));
      const axis = $target.attr('data-axis');

      if (axis === 'col') {
        toggleReader([], [headerId]);
      } else if (axis === 'row') {
        toggleReader([headerId], []);
      }
    });

    // dynamically calculate and adjust the elements position to always draw it within the window's bounds
    const overlayHeight = $attributeTooltip.height();
    const overlayWidth = $attributeTooltip.width();
    const pageHeight = $window.height();
    const pageWidth = $window.width();

    let top = pageY;
    let left = pageX;

    if ((overlayWidth + left) > pageWidth) {
      left -= overlayWidth - 10;
    } else {
      left += 10;
    }

    if ((overlayHeight + top) > pageHeight) {
      top -= overlayHeight - 10;
    } else {
      top += 10;
    }

    $attributeTooltip.css({
      top: top,
      left: left
    });

    return true;
  }

  /**
   * Handles the table click to show the reader dialog.
   */
  function handleTableClick() {
    //#region Header Click shows popup
    // when clicking the row (i.e - side headers)
    $('.clickable-row').on('click', (e) => {
      const $target = $(e.currentTarget);
      const headerId = $target.data('id');
      const createdPopup = createExtUrlPopup('row', headerId, e.pageX, e.pageY);

      if (!createdPopup) {
        toggleReader([headerId], []);
      }
    });

    // when clicking the column (i.e - top headers)
    $('.clickable-col').on('click', (e) => {
      const $target = $(e.currentTarget);
      const headerId = $target.data('id');
      const createdPopup = createExtUrlPopup('col', headerId, e.pageX, e.pageY);

      if (!createdPopup){
        toggleReader([], [headerId]);
      }
    });
    //#endregion

    $('.cell').on('click', (e) => {
      const $target = $(e.currentTarget);
      const totalCount = $target.data('totalCount');

      if (totalCount === 0) {
        return;
      }

      let colIds = $target.data('colid');
      let rowIds = $target.data('rowid');

      if (isNaN(colIds)) {
        colIds = colIds.split(',').map(id => parseInt(id));
      } else {
        colIds = [colIds]
      }

      if (isNaN(rowIds)) {
        rowIds = rowIds.split(',').map(id => parseInt(id));
      } else {
        rowIds = [rowIds]
      }

      toggleReader(rowIds, colIds);
    });
  }

  /**
   *  handle the about button click to show the about map reader dialog
   */
  function handleAboutClick() {
    $('.menu-about').on('click', e => {
      let aboutHtml = '<div class="title clearfix">' +
        '<button class="btn close" aria-label="Close about" >X</button> <span>About This Map</span>' +
        '</div>' +
        '<div class="content">' +
        '<div class="read">' + aboutContent + '</div>' +
        '</div>';

      $reader.html(aboutHtml);

      $('.close', $reader).on('click', () => {
        closeReader();
        $announce.html('About this map closed.');
      });

      $reader.css({display: 'block'});
      $veil.addClass('open');
      $reader.addClass('open');
      readerFocusTrap.activate();

      // Close modal on escape key
      $reader.on('keydown', function (event) {
        if (event.key === "Escape") {
          closeReader();
        }
      });

      $announce.html('About this map opened.');
    });
  }

  /**
   *  handle the accessibility button click to show the accessibility dialog
   */
  function handleAccessiblityClick() {
    $('.menu-accessibility').on('click', e => {
      $('.close', $accessibility).on('click', () => {
        $accessibility.removeClass('open');
        $veil.removeClass('open');
        $accessibility.css({display: 'none'});
        accessibilityFocusTrap.deactivate();
        $announce.html('Accessibility closed.');
      });

      $accessibility.css({display: 'block'});
      $veil.addClass('open');
      $accessibility.addClass('open');
      accessibilityFocusTrap.activate();

      // Close modal on escape key
      $accessibility.on('keydown', function (event) {
        if (event.key === "Escape") {
          $accessibility.removeClass('open');
          $veil.removeClass('open');
          $accessibility.css({display: 'none'});
          accessibilityFocusTrap.deactivate();
        }
      });

      $announce.html('Accessibility opened.');
    });
  }

  /**
   * Handles the study submission click to show the information on how to
   * submit a new study to the map.
   */
  function handleStudySubmissionClick() {
    $('.menu-studysubmit').on('click', e => {
      let studySubmitHtml =
      '<div class="title clearfix">' +
        '<button class="btn close" aria-label="Close submit a study" >X</button> <span> Submit a Study </span>' +
      '</div>' +
      '<div class="content">' +
        '<div class="read">' + studySubmissionContent + '</div>' +
      '</div>';

      $reader.html(studySubmitHtml);

      $('.close', $reader).on('click',() => {
        closeReader();
        $announce.html('Submit a study closed.')
      });

      $reader.css({display: 'block'});
      $veil.addClass('open');
      $reader.addClass('open');
      readerFocusTrap.activate();

      // Close modal on escape key
      $reader.on('keydown', function (event) {
        if (event.key === "Escape") {
          closeReader();
        }
      });

      $announce.html('Submit a study opened.');
    });
  }

  /**
   * Makes the headers hide/show.
   */
  function handleExpandClick() {
    const $menuExpand = $('.menu-expand');
    const $topTable = $('table', $topHead);
    const $sideTable = $('table', $sideHead);

    $menuExpand.on('click', e => {

      if ($topTable.find('.collapsed').length > 0 || $sideTable.find('.collapsed').length > 0) {
        alert('You cannot hide the headers when they are collapsed.');
        return;
      }

      $menuExpand.toggleClass('active');
      
      if ($menuExpand.hasClass('active')) {
        $topTable.height('auto');
        $sideTable.width('auto');
        $('.inactive-text').attr('aria-hidden', 'true');
        $('.active-text').attr('aria-hidden', 'false');
      } else {
        $topTable.height(topColHeight);
        $sideTable.width(sideColWidth);
        $('.inactive-text').attr('aria-hidden', 'false');
        $('.active-text').attr('aria-hidden', 'true');
      }

      $('.header, .header-can-hide').slideToggle(200, function () {
          adjustTable();
      });
    });
  }

  /**
   * Toggles fullscreen mode.
   */
  function handleFullscreenClick() {
    const $menuFullscreen = $('.menu-fullscreen');

    $menuFullscreen.on('click', e => {
      toggleFullScreen();
      $menuFullscreen.toggleClass('active');

      if ($menuFullscreen.hasClass('active')) {
        $('.inactive-text').attr('aria-hidden', 'true');
        $('.active-text').attr('aria-hidden', 'false');
      } else {
        $('.inactive-text').attr('aria-hidden', 'false');
        $('.active-text').attr('aria-hidden', 'true');
      }
    });
  }

  /**
   * Toggles reader mode.
   */
  function handleReaderClick() {
    const $menuReader = $('.menu-reader');

    const colIdList = csvData.rows[csvData.totalColDepth - 1].map(item => item.id)
    const rowIdList = []

    for (let i = csvData.totalColDepth; i < csvData.rows.length; i++) {
      const row = csvData.rows[i]
      rowIdList.push(row[row.length - 1].id)
    }

    $menuReader.on('click', e => {
      toggleReader(rowIdList, colIdList);
      $menuReader.toggleClass('active');
    });
  }

  /**
   * Toggles the column collapse.
   * @param miss
   * @param count
   */
  function toggleTopColCollapse(miss, count) {
    const max = miss + count;

    $('.top-head tr').each((rowIndex, row) => {
      if (rowIndex <= 1) return;
      let total = 0;

      $(row).children().each((colIndex, cell) => {
        const $cell = $(cell);
        const colSpan = parseInt($cell.attr('colspan'));
        total += colSpan;

        if (total > miss && total <= max) {
          if (total - 1 === miss) {
            $cell.toggleClass('first');
          }

          if (total - 1 === max) {
            $cell.toggleClass('last');
          }

          $cell.toggleClass('collapsed');
        } else if (total > max) {
          return false;
        }
      });
    });

    buildTableRows();
    adjustTable();

    $pivotBody.trigger('scroll');

    // Update data in the table.
    updateReferenceCounts();
    updateTableDataView();
  }

  /**
   * Toggles the row collapse.
   * @param miss
   * @param count
   */
  function toggleSideColCollapse(miss, count) {
    const max = miss + count;
    let total = 0;

    $('.side-head .level-2').each((index, cell) => {
      const $cell = $(cell);
      const rowSpan = parseInt($cell.attr('rowspan'));
      total += rowSpan;

      if (total > miss && total <= max) {
        if (total - 1 === miss) {
          $cell.toggleClass('first');
        }

        if (total - 1 === max) {
          $cell.toggleClass('last');
        }

        $cell.toggleClass('collapsed')
      } else if (total > max) {
        return false;
      }
    });

    total = 0;

    $('.side-head .level-3').each((index, cell) => {
      const $cell = $(cell);
      const rowSpan = parseInt($cell.attr('rowspan'));
      total += rowSpan;

      if (total > miss && total <= max) {
        if (total - 1 === miss) {
          $cell.toggleClass('first');
        }

        if (total - 1 === max) {
          $cell.toggleClass('last');
        }

        $cell.toggleClass('collapsed')
      } else if (total > max) {
        return false;
      }
    });

    buildTableRows();
    adjustTable();

    $pivotBody.trigger('scroll');

    // Update data in the table.
    updateReferenceCounts();
    updateTableDataView();
  }

  /**
   * Collapse all the rows and columns in the map.
   */
  function collapseAll(){
    if (collapseColumnHeaders)
    {
      const $colHeaders =  $('.level-1')
        .filter(function() {
          return this.colSpan > 1;
        });

      $colHeaders.each((index, cell) => {
        const $cell = $(cell);
        
        $cell.toggleClass('collapsed');
        const count = parseInt($cell.attr('colspan'));
        let miss = 0;

        let $prev = $cell.prev();

        while ($prev.length > 0) {
          try {
            miss += parseInt($prev.attr('colspan'))
            $prev = $prev.prev();
          }
          catch (e) {
            break;
          }
        }

        if (count > 0) {
            toggleTopColCollapse(miss, count);
        }
      });
    }

    if (collapseRowHeaders)
    {
      const $rowHeaders =  $('.level-1').filter(function() {
        return this.rowSpan > 1;
      });

      $rowHeaders.each((index, cell) => {
        const $cell = $(cell);
        $cell.toggleClass('collapsed');

        const count = parseInt($cell.attr('rowspan'));
        let miss = 0;
        $('.side-head .level-1').each((index, otherCell) => {
          const $otherCell = $(otherCell);

          if ($otherCell.text() !== $cell.text()) {
            miss += parseInt($otherCell.attr('rowspan'));
          } else {
            return false;
          }
        });

        if (count > 0) {
            toggleSideColCollapse(miss, count);
        }
      });
    }
  }

  /**
   * Toggles collapsing columns and rows.
   */
  function handleTableRowColCollapse() {
    // Manage column collapse.
    $('.btnColCollapse').on('click', e => {
      const $target = $(e.currentTarget);
      const $cell = $target.parent().parent();
      $cell.toggleClass('collapsed');
      $cell.toggleClass('busy');

      const count = parseInt($cell.attr('colspan'));
      let miss = 0;

      let $prev = $cell.prev();

      while ($prev.length > 0) {
        try {
          miss += parseInt($prev.attr('colspan'))
          $prev = $prev.prev();
        }
        catch (e) {
          break;
        }
      }

      if (count > 0) {
        setTimeout(() => {
          toggleTopColCollapse(miss, count);
          $cell.toggleClass('busy');
        }, 50);
      } else {
        $cell.toggleClass('busy');
      }
    });

    // Manage row collapse.
    $('.btnRowCollapse').on('click', e => {
      const $target = $(e.currentTarget);
      const $cell = $target.parent().parent();
      $cell.toggleClass('collapsed');
      $cell.toggleClass('busy');

      const count = parseInt($cell.attr('rowspan'));
      let miss = 0;

      $('.side-head .level-1').each((index, cell) => {
        const $otherCell = $(cell);

        if ($otherCell.text() !== $cell.text()) {
          miss += parseInt($otherCell.attr('rowspan'));
        } else {
           return false;
        }
      });

      if (count > 0) {
        setTimeout(() => {
          toggleSideColCollapse(miss, count);
          $cell.toggleClass('busy');
        }, 50);
      } else {
        $cell.toggleClass('busy');
      }
    });
  }

  /**
   * Adjusts the table as the window is resized.
   */
  function adjustTable() {
    const bodyWidth = $pivotTable.width() - $sideHead.width();
    const topHeadWrapperCssHeight = $topHead.height();
    const topHeadWrapperCssPaddingLeft = $sideHead.width();
    const topHeadCssWidth = bodyWidth;
    const bodyCssWidth = bodyWidth - 1;
    let sideHeadCssHeight = $window.height() - $topHead.height() - $footer.height() - $menu.height() - 48;
    let bodyCssHeight = sideHeadCssHeight;

    $header = $('.header')

    if ($header.length > 0 && $header.css('display') !== 'none') {
      sideHeadCssHeight = sideHeadCssHeight - $header.height() - 8;
      bodyCssHeight = sideHeadCssHeight;
    }

    $topHeadWrapper.css({
      'height': topHeadWrapperCssHeight,
      'padding-left': topHeadWrapperCssPaddingLeft
    });

    $topHead.css({
      'width': topHeadCssWidth
    });

    $topHeadTable.css({
      'margin-left': '0px'
    });

    $sideHead.css({
      'height': sideHeadCssHeight
    });

    $sideHeadTable.css({
      'margin-top': '0px'
    });

    $pivotBody.css({
      overflow: 'scroll',
      width: bodyCssWidth,
      height: bodyCssHeight
    });

    $pivotBody.scroll(function (e) {
      $topHeadTable.css({
        'margin-left': e.target.scrollLeft * -1
      });

      $sideHeadTable.css({
        'margin-top': e.target.scrollTop * -1
      });
    });
  }

  function UpdateRecordCount() {
    if (!showRecordCount) return;

    const colIdList = csvData.rows[csvData.totalColDepth - 1].map(item => item.id)
    const rowIdList = []

    for (let i = csvData.totalColDepth; i < csvData.rows.length; i++) {
      const row = csvData.rows[i]
      rowIdList.push(row[row.length - 1].id)
    }

    const references = getFilteredReferences(rowIdList, colIdList);
    $recordCount.html('(' + references.length + ')');
  }

  // Call all the methods to initialize the page.
  createSettingsPanel();
  setupStyleSwitch();
  buildTable();
  adjustTable();
  buildLegend();
  handleExpandClick();
  handleFullscreenClick();
  handleReaderClick();
  handleTableRowColCollapse();
  handleAccessiblityClick();

  // Update the record count on first load.
  UpdateRecordCount();

  if(collapseColumnHeaders || collapseRowHeaders) {
    collapseAll();
  }

  if (aboutContent.trim().length === 0) {
    $('.menu-about').hide();
  }
  else {
    handleAboutClick();

    if (aboutPopup) {
      $('.menu-about').trigger('click');
    }
  }

  if (studySubmissionContent.trim().length === 0) {
    $('.menu-studysubmit').hide();
  } else {
    handleStudySubmissionClick();
  }

  // Show the loader.
  const $loader = $('.loader');
  const windowHeight = $window.height() + 200;

  $window.resize(adjustTable);

  // Slide the up after all is done.
  $loader
    .css({
      'top': -windowHeight,
      'bottom': windowHeight
    });

  // Removes the loader after the animation is complete.
  setTimeout(() => {
    $loader.remove();
  }, 2000);
});

  </script>
  <script src="https://unpkg.com/@popperjs/core@2"></script>
  <script src="https://unpkg.com/tippy.js@6"></script>
  <script>
    tippy('[data-tippy-content]');
  </script>
</body>

</html>